Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
This variantScenario
BenignPathogenic
Likely pathogenic.A likely pathogenic classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
About BRCA1
BRCA1 encodes a large nuclear protein that helps maintain genomic stability by coordinating the repair of DNA double-strand breaks through homologous recombination, and it also regulates transcription and the cell cycle. It acts as a tumor suppressor, working with proteins such as RAD51, BRCA2, BARD1, and PALB2 to preserve genome integrity. Inherited alterations in BRCA1 cause hereditary breast and ovarian cancer syndrome, with elevated risks of breast, ovarian, prostate, and pancreatic cancers, and biallelic loss underlies a rare form of Fanconi anemia. Because BRCA1-driven tumors rely on impaired DNA repair, they are treatable with PARP inhibitors.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen BRCA1 VCEP v1.2. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Met (Very Strong): this nonsense change creates a premature stop, p.(Lys463Ter), predicted to trigger nonsense-mediated decay well upstream of the final exon.
PM2Supporting
PM2 · supporting
Met (Supporting): the variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
Likely Pathogenic from two applicable criteria: PVS1 (Very Strong, predicted nonsense-mediated decay) and PM2 (Supporting, absent from population databases).
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
ACMG/AMP criteria under ClinGen BRCA1 VCEP v1.2, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 2 not met · 12 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
PVS1 applied at Very Strong strength: nonsense variant c.1387A>T (p.Lys463Ter) in BRCA1, a gene with an ENIGMA VCEP-confirmed germline LOF disease mechanism, positioned in a large internal exon (c.671-4096) well upstream of the terminal exon, predicted to trigger NMD per standard PVS1 positional rules and consistent with ENIGMA Table 4 exon-level PVS1 applicability for this exon.
PM4 and BP3 are not applicable to this variant: both criteria evaluate protein-length-altering in-frame indels or stop-loss variants, whereas c.1387A>T is a nonsense/stop-gain substitution evaluated instead under PVS1. This is also consistent with the ENIGMA BRCA1/2 VCEP cspec explicitly designating both PM4 and BP3 as Not Applicable for this gene/framework.
PS2 and PM6 are explicitly designated 'Not Applicable' by the governing ClinGen ENIGMA BRCA1/BRCA2 Expert Panel Specification v1.2, which supersedes generic ACMG/AMP de novo criteria for this gene.
PP1 and BS4 remain applicable criteria under ENIGMA v1.2 (quantitative cosegregation LR method, Appendix I) but no pedigree, cosegregation, or family-history segregation data of any kind was retrieved for this variant in the case bundle; both are returned as not_assessed pending such data.
Variant NM_007294.4:c.1387A>T / NP_009225.1:p.(Lys463Ter) is a nonsense (PTC-generating) variant, not a missense or synonymous substitution.
The ClinGen ENIGMA BRCA1/2 v1.2 CSpec restricts the PS3/BS3 functional-assay evidence pathway (Specifications Table 9, Supplementary Table ST4 mammalian functional assay dataset) to missense and synonymous variant types; loss-of-function/truncating variants are instead evaluated for functional confirmation via the PVS1(RNA) / BP7(RNA) mRNA-assay pathway, which is outside this PS3/BS3 criterion group's scope.
No functional assay entry specific to c.1387A>T was located in ENIGMA Table 9, Supplementary Table ST4, or any other source in the evidence bundle.
Both PS3 and BS3 are therefore assessed as not_applicable for this variant under the governing VCEP specification.
This variant, NM_007294.4:c.1387A>T (p.(Lys463Ter)), is absent from ClinVar entirely (no record found), which forecloses PP5 and BP6 under both the ENIGMA VCEP 'Not Applicable' designation and the exact-variant expert-panel requirement.
PS4 requires case-control enrichment data (OR/p-value or LR) that was not retrieved for this variant in gnomAD, ClinVar, or the literature bundle; PS4 is left not_assessed rather than not_met because absence of retrieved data is not equivalent to a demonstrated absence of enrichment.
PP4/BP5 both depend on an exact HGVS-matched row in the Li et al. 2020 (PMID:31853058) clinical-history LR table, which was not present for this variant in the consolidated evidence bundle; both are left not_assessed pending a direct spreadsheet lookup.
PM3 could not be assessed: the ENIGMA v1.2 CSpec confines PM3 to a Fanconi-Anemia-specific biallelic co-occurrence pathway, and no proband case report, zygosity, phasing, or FA phenotype data for this variant exists anywhere in the case-evidence bundle; ClinVar has no entry for this variant.
BP2 is marked not_applicable per the explicit ENIGMA BRCA1/2 v1.2 CSpec designation (applicability: Not Applicable), which takes precedence over generic ACMG BP2.
NM_007294.4:c.1387A>T is NP_009225.1:p.(Lys463Ter), a nonsense (premature termination codon) variant, not missense, synonymous, or intronic.
The ENIGMA BRCA1/BRCA2 v1.2 specification's calibrated bioinformatic-evidence rules for PP3, BP4, and BP7 are explicitly scoped by variant type to missense/in-frame indel (BayesDel no-AF), silent, and intronic variants; nonsense/PTC variants are excluded from all three rule sets, with the truncating mechanism instead assessed under PVS1 by a different criteria group.
SpliceAI predicts no meaningful splice impact (max delta score = 0.001, far below both the PP3 pathogenic-supporting threshold of >=0.2 and would-be BP4 benign-supporting threshold of <=0.1), so even under a hypothetical splicing-path analysis no PP3/BP4 code would be triggered.
A local BayesDel no-AF score (0.60222) exists in the source registry but is not used for PP3/BP4 because it falls under the missense/in-frame protein-effect pathway, which this nonsense variant does not qualify for; applying it would double-count the loss-of-function mechanism already captured by PVS1.
All three criteria in this group are therefore returned as not_applicable rather than met/not_met, since the variant type places it outside the scope of the governing VCEP's PP3/BP4/BP7 rules.
Variant NM_007294.4:c.1387A>T (p.(Lys463Ter)) is absent from all three population databases queried (gnomAD v2.1 exome, gnomAD v4.1, gnomAD-Canada v1.0), across both GRCh37 and GRCh38 coordinates.
Absence supports PM2_Supporting per ENIGMA BRCA1/2 CSpec v1.2 and precludes both BA1 and BS1 (which require FAF above defined thresholds).
BS2 could not be assessed due to lack of proband-level Fanconi Anemia phenotype/zygosity data required by the ENIGMA Table 8 point-scoring approach; flagged for human review.
No criteria match.
Met · 2
PVS1Very strongMet (Very Strong): this nonsense change creates a premature stop, p.(Lys463Ter), predicted to trigger nonsense-mediated decay well upstream of the final exon.
Details ▾Hide ▴
Reasoning
NM_007294.4:c.1387A>T is a nonsense substitution producing NP_009225.1:p.(Lys463Ter), a premature termination codon located in the large BRCA1 coding exon spanning c.671-4096 (legacy exon 11, ENIGMA Table 4 designation E10(11)). This PTC is far upstream of the final exon (23 total transcript segments follow), so under the standard PVS1/NMD position rule (PTC not in the last exon and not within the last 50 bp of the penultimate exon) the transcript is predicted to trigger nonsense-mediated decay. Germline loss of function is an established BRCA1 disease mechanism per the ENIGMA VCEP cspec, which supplies an explicit PVS1 rule (Very Strong/Strong/Moderate/Supporting tiers keyed to exon-level decision Table 4) and whose gene-level PVS1 gate is 'eligible' with lof_mechanism_supported=true. ENIGMA Table 4 lists exon E10(11) among exons where null/PTC variants and PM5_PTC are applicable (i.e. not flagged PVS1_N/A), consistent with full Very Strong PVS1 weight for a nonsense variant in this exon. There is no indication this exon is dispensable, subject to common in-frame skipping, or enriched for population-observed LoF variation that would argue for downgrade.
Rule
PVS1_VeryStrong: null (nonsense) variant in BRCA1, a gene with an established germline LOF disease mechanism (ENIGMA cspec); PTC predicted to trigger NMD (not located in the terminal exon or last 50bp of the penultimate exon) and not in an exon flagged as PVS1_N/A.
Evidence considered
case_summary.json cspec block: PVS1 defaultStrength 'Pathogenic Very Strong'; rule text: 'Null variant (nonsense, frameshift, splice site...) in a gene where loss of function (LOF) is a known mechanism of disease. Apply at appropriate strength according to PVS1 flowchart... See Specifications Table 4 and Appendix D for details.'
pvs1_gene_context.json: gene=BRCA1, germline_disease_context_found=true, lof_mechanism_supported=true, pvs1_gene_gate='eligible', mechanism_rationale citing official CSPEC/VCEP PVS1 guidance for BRCA1.
pvs1_variant_assessment.json: consequence_class='nonsense', variant_bucket='nonsense', suggested_default_strength='PVS1', protein change NP_009225.1:p.(Lys463Ter).
prefetch.json mutalyzer selector_short exon/CDS coordinate map: c.1387 falls within the c.671-4096 exon segment, the 10th of 23 total transcript segments, confirming the PTC is well upstream of the terminal exon/3'UTR segment (c.5468-*1383), supporting an NMD-predicted outcome.
Specifications_Table4_V1.2_2024-11-18.xlsx summary: 'PM5_PTC applicable exons for BRCA1' list includes 'E10(11)', indicating this exon is treated as a standard null-variant/PTC-bearing exon (not PVS1_N/A) in the ENIGMA decision table.
SupplementaryTables_V1.2_2024-11-18.xlsx ST4 excerpt row for BRCA1 c.4986+3G>T shows the ENIGMA table records PTC_NMD status per variant, confirming NMD prediction is a standard field considered in this VCEP framework's PVS1/PM5 workflow.
Still missing
The gene-specific extract of Specifications_Table4_V1.2_2024-11-18.xlsx available in this bundle only shows rows for exon 1/2; the exact per-exon PVS1 strength row for E10(11) was not individually visualized, so exon-level applicability was inferred from the PM5_PTC-applicable exon list (which includes E10(11)) and the absence of a PVS1_N/A flag for that exon, rather than a directly read PVS1 strength cell.
No variant-specific RNA/NMD experimental data (e.g. patient mRNA or minigene assay) were identified for c.1387A>T; the NMD prediction relies on the standard positional rule rather than direct transcript-level confirmation.
PM2SupportingMet (Supporting): the variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases.
Details ▾Hide ▴
Reasoning
ENIGMA PM2 (Supporting only) applies when the variant is absent from controls in an outbred population, from gnomAD v2.1 (non-cancer, exome only subset) and gnomAD v3.1 (non-cancer), with region read depth >=25. The variant NM_007294.4:c.1387A>T is absent from gnomAD v2.1 exomes and gnomAD v4.1 (which incorporates v3.1 genome data), and also absent from the supplementary gnomAD-Canada v1.0 dataset, consistent across two independent genome builds (GRCh37/GRCh38). This satisfies the absence criterion for PM2_Supporting. Read depth at this position was not independently confirmed in the retrieved evidence, which is a minor gap but does not undermine met status given consistent absence across three independent large population databases.
Rule
ENIGMA BRCA1/2 CSpec v1.2 PM2: Supporting if absent from gnomAD v2.1 (non-cancer exome only subset) and gnomAD v3.1 (non-cancer) controls, with average read depth >=25 at the variant position.
Evidence considered
gnomAD v2.1 (exome, non-cancer subset) search for 17-41246161-T-A returned absent, found=false.
gnomAD v4.1 search for chr17-43094144-T-A returned absent, found=false.
gnomAD-Canada v1.0 (HostSeq genomes) API query for 17-43094144-T-A returned absent, found=false.
ENIGMA BRCA1/2 CSpec v1.2 PM2 rule: absent from controls in outbred population from gnomAD v2.1 (non-cancer exome) and gnomAD v3.1 (non-cancer), with region average read depth >=25, applied at Supporting strength only.
Still missing
Region-level average read depth (>=25x requirement per CSpec) at chr17:43094144 was not directly confirmed from the gnomAD coverage track in the retrieved evidence.
BA1Not met: the variant is completely absent from population databases, far below the >0.1% frequency threshold.
Details ▾Hide ▴
Reasoning
Per ENIGMA BRCA1/2 CSpec v1.2, BA1 requires filter allele frequency (FAF) > 0.1% in gnomAD v2.1 (non-cancer exome subset) and/or gnomAD v3.1 (non-cancer). The variant NM_007294.4:c.1387A>T (NC_000017.11:g.43094144T>A) is absent from gnomAD v2.1 exomes, gnomAD v4.1 (which includes v3.1 genomes), and gnomAD-Canada v1.0. An absent variant has an FAF of 0 (well below 0.1%), so BA1 is not met.
Rule
ENIGMA BRCA1/2 CSpec v1.2 BA1: Stand Alone if FAF > 0.1% in gnomAD v2.1 (non-cancer exome) and/or gnomAD v3.1 (non-cancer), non-founder population(s).
Evidence considered
gnomAD v2.1 (exome, non-cancer subset) query for 17-41246161-T-A returned search_status=absent, found=false.
gnomAD v4.1 query for chr17-43094144-T-A returned search_status=absent, found=false.
gnomAD-Canada v1.0 (HostSeq genomes) API query for 17-43094144-T-A returned search_status=absent, found=false.
BS1Not met: the variant is absent from population databases, well below the >0.01% frequency threshold.
Details ▾Hide ▴
Reasoning
ENIGMA BS1 requires FAF > 0.01% (Strong) or > 0.002% and <= 0.01% (Supporting) in gnomAD v2.1 exome non-cancer and/or gnomAD v3.1 non-cancer, non-founder population(s). The variant is absent from gnomAD v2.1 exomes, gnomAD v4.1, and gnomAD-Canada v1.0, giving an FAF of 0, which is below all BS1 thresholds. BS1 is not met.
Rule
ENIGMA BRCA1/2 CSpec v1.2 BS1: Strong if FAF > 0.01% (0.0001); Supporting if FAF > 0.002% and <= 0.01%, in gnomAD v2.1 exome non-cancer and/or gnomAD v3.1 non-cancer, non-founder population(s).
Evidence considered
gnomAD v2.1 exome and gnomAD v4.1 both report search_status=absent for this variant.
PS1Not assessed: insufficient evidence was available to evaluate this criterion.
Details ▾Hide ▴
Reasoning
PS1 could not be assessed because its agent did not produce valid output.
Still missing
attempt 1: Hermes timed out after 200s and left no usable output_file
attempt 2: Hermes timed out after 200s and left no usable output_file
attempt 3: Hermes timed out after 200s and left no usable output_file
PS4Not assessed: no case-control enrichment or odds-ratio data for this exact variant were available.
Details ▾Hide ▴
Reasoning
ENIGMA BRCA1/2 v1.2 defines PS4 (Strong) as case-control enrichment: p<=0.05 and OR>=4 (lower CI excludes 2.0), or the VCEP-preferred multifactorial case-control LR approach (instructionsToUse notes LR estimates should be used in preference to OR data, under PP4/BP5 rather than proband counting). No case-control study, cohort enrichment statistic, or variant-specific OR/LR data for NM_007294.4:c.1387A>T was retrieved in this case's evidence bundle. ClinVar search returned no result for this variant (absent from ClinVar), gnomAD v2.1/v4.1/Canada all show the variant absent, and no case-control or cohort-frequency literature was found/extracted. The ENIGMA ST15 case-control table only covers gene-level (not variant-level) BP7 comparisons and does not include this variant.
Rule
PS4_Strong: case-control p<=0.05 and OR>=4 (lower CI excludes 2.0), per ENIGMA BRCA1/2 Specifications v1.2 (cspec).
Evidence considered
ClinVar search for BRCA1 c.1387A>T returned no result (evidence_sentence: 'This variant is absent from ClinVar').
gnomAD v2.1, v4.1, and gnomAD-Canada v1.0 all report the variant as absent, so no case-control frequency comparison could be constructed from population resources.
ENIGMA BRCA1/2 Specifications v1.2 PS4 rule requires case-control p<=0.05 and OR>=4, or preferentially a case-control LR under PP4/BP5; no such variant-level dataset was located for this variant.
Still missing
No case-control cohort data (cases vs controls, OR, p-value, or LR) specific to c.1387A>T was found in ClinVar, prefetch, or literature_pass records.
No prior-observation-in-multiple-unrelated-patients data (Note 2 rare-variant fallback) was retrieved for this variant.
PM1Not assessed: insufficient evidence was available to evaluate this criterion.
Details ▾Hide ▴
Reasoning
PM1 could not be assessed because its agent did not produce valid output.
Still missing
attempt 1: Hermes timed out after 200s and left no usable output_file
attempt 2: Hermes timed out after 200s and left no usable output_file
attempt 3: Hermes timed out after 200s and left no usable output_file
PM3Not assessed: no proband case report or phasing data linking this variant to a second pathogenic variant were available.
Details ▾Hide ▴
Reasoning
ENIGMA BRCA1/2 v1.2 CSpec restricts PM3 solely to the Fanconi Anemia (FA) biallelic pathway: co-occurrence of NM_007294.4:c.1387A>T with a second pathogenic BRCA1/2 variant in a patient with an FA-consistent phenotype (chromosome breakage findings and/or FA clinical features per Specifications Table 6). No proband-level clinical case report for this variant was located anywhere in the case-evidence bundle (ClinVar search returned no_result/absent; no literature identifying an affected carrier; no trans/cis phasing data; no chromosome-breakage or FA phenotype data). Without any observed proband or phase information, PM3 cannot be evaluated.
ENIGMA BRCA1/2 v1.2 CSpec (case_summary.json cspec.criteria PM3 rules) restricts PM3 application to patients with a phenotype consistent with BRCA1/BRCA2-related Fanconi Anemia who carry co-occurrent variants in the same gene, scored via Specifications Table 6 (Supporting=1pt, Moderate=2pt, Strong>=4pt)
ClinVar search for BRCA1 c.1387A>T returned search_status 'no_result', found:false, with evidence_sentence 'This variant is absent from ClinVar' -- no clinical submission, zygosity, or co-occurrence data available from this source
No proband/case report, pedigree, phasing, or chromosome-breakage data for this variant was found anywhere in the consolidated case-evidence bundle (review_manifest, case_summary, source_registry, prefetch, evidence, literature_pass, vcep_materials, fulltext_map, paper_extracts)
Still missing
No case report or clinical database record identifying any individual carrying this variant, so zygosity/phase relative to a second BRCA1/2 pathogenic variant is unknown
No chromosome breakage (DEB/MMC) or Fanconi Anemia phenotype data available to assess the FA-specific PM3 threshold defined by the ENIGMA v1.2 specification
ClinVar has no entry for this variant (search_status: no_result), removing the most likely source of co-occurrence/zygosity data
PM5Not assessed: insufficient evidence was available to evaluate this criterion.
Details ▾Hide ▴
Reasoning
PM5 could not be assessed because its agent did not produce valid output.
Still missing
attempt 1: Hermes timed out after 200s and left no usable output_file
attempt 2: Hermes timed out after 200s and left no usable output_file
attempt 3: Hermes timed out after 200s and left no usable output_file
PP1Not assessed: no family segregation or pedigree data for this variant were available.
Details ▾Hide ▴
Reasoning
The ENIGMA v1.2 specification defines PP1 for BRCA1 using a quantitative co-segregation LR (Supporting >=2.08, Moderate >=4.3, Strong >=18.7, Very Strong >=350) per Appendix I. No pedigree, family segregation data, affected-relative genotyping, or a quantitative cosegregation analysis for c.1387A>T (p.Lys463Ter) is present anywhere in this case's evidence bundle (evidence.json, literature_pass.json, vcep_materials.json, or fulltext_map). The literature identified (OncoKB functional papers, guideline/statement papers on BRCA screening) contains no family/pedigree or segregation content and none report this specific variant in a segregation context.
Evidence considered
Case-evidence bundle (evidence.json, literature_pass.json, vcep_materials.json, fulltext_map.json, paper_extracts.json) contains no pedigree, family-segregation, or cosegregation-LR data for NM_007294.4:c.1387A>T; the ENIGMA cspec Appendix I quantitative method required for PP1 cannot be applied without such data.
Still missing
No pedigree or multi-affected-family segregation data available for this variant.
No quantitative co-segregation LR (per ENIGMA Appendix I) has been calculated or reported for this variant.
Would need a segregation study or clinical lab pedigree report specifically citing c.1387A>T to assess PP1.
PP2Not assessed: insufficient evidence was available to evaluate this criterion.
Details ▾Hide ▴
Reasoning
PP2 could not be assessed because its agent did not produce valid output.
Still missing
attempt 1: Hermes timed out after 200s and left no usable output_file
attempt 2: Hermes timed out after 200s and left no usable output_file
attempt 3: Hermes timed out after 200s and left no usable output_file
PP4Not assessed: no variant-specific clinical or family-history likelihood-ratio data were available.
Details ▾Hide ▴
Reasoning
ENIGMA v1.2 restricts PP4 to a combined clinical-history likelihood ratio (LR) derived from the Li et al. 2020 (PMID:31853058) personal/family-history model, looked up by exact Gene=BRCA1 and HGVS_Nucleotide match in the gene-specific clinical_history_LR.xlsx (PP4 thresholds: Supporting LR>=2.08, Moderate>=4.3, Strong>=18.7, Very Strong>=350). The consolidated evidence bundle for this case does not contain a variant-level LR row for c.1387A>T from that table (the only rows visible in the bundle's extracted sheet content are for other variants, e.g. c.197A>G and c.4986+3G>T). No proband-specific personal/family-history data, clinical-history LR, or Easton et al. 2007 multifactorial output specific to this variant was retrieved.
Rule
PP4: combined clinical-history LR per ENIGMA BRCA1/2 Specifications v1.2 Table 7 (Li et al. 2020, PMID:31853058) (cspec).
Evidence considered
ENIGMA BRCA1/2 Specifications v1.2 restricts PP4 to combined clinical-history LR data (Table 7 thresholds: Supporting LR>=2.08, Moderate>=4.3, Strong>=18.7, Very Strong>=350), sourced from the Li et al. 2020 (PMID:31853058) clinical-history LR model per the VCEP file index guidance.
The clinical_history_LR.xlsx extract present in this case's evidence bundle contains rows for other BRCA1 variants (e.g. c.197A>G, c.4986+3G>T) but no row matching NM_007294.4:c.1387A>T, so no LR value for this specific variant could be retrieved.
Still missing
No exact-match row for NM_007294.4:c.1387A>T was located in the Li 2020 (PMID:31853058) clinical-history LR table within the evidence bundle; a direct lookup against the source spreadsheet is needed before PP4 can be scored.
No case-level personal/family-history phenotype data for the individual(s) carrying this variant was supplied in the case bundle.
BS2Not assessed: no carrier phenotype or zygosity data were available to evaluate this criterion.
Details ▾Hide ▴
Reasoning
ENIGMA BS2 for BRCA1/2 is scored via a points-based proband-level table (Specifications Table 8) assessing absence of Fanconi Anemia phenotype features in individuals carrying this variant (relevant to biallelic/homozygous observations). No proband-level clinical or zygosity data for carriers of this variant, and no homozygote counts, are present in the case bundle. The variant is entirely absent from gnomAD v2.1, v4.1, and gnomAD-Canada, so no homozygous or biallelic observations exist in these population datasets either. There is insufficient information (no Table 8 proband data) to compute a BS2 point total.
Rule
ENIGMA BRCA1/2 CSpec v1.2 BS2: Applied in absence of features of recessive disease (Fanconi Anemia phenotype) per Specifications Table 8 point scoring; thresholds Strong >=4 points, Moderate = 2 points, Supporting = 1 point.
Evidence considered
Variant is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, so zero homozygotes are observed in these cohorts (uninformative for BS2 scoring, not evidence of benignity).
ENIGMA BS2 rule requires proband-level Fanconi Anemia phenotype absence/presence data scored via Specifications Table 8, which is not available in the case bundle for this variant.
Still missing
No access to ENIGMA Specifications Table 8 proband-level scoring data for this specific variant.
No reported homozygous/biallelic carriers or associated phenotype data (absence/presence of Fanconi Anemia features) in any source consulted.
BS4Not assessed: no family segregation data showing non-segregation were available.
Details ▾Hide ▴
Reasoning
The ENIGMA v1.2 specification defines BS4 using the same quantitative co-segregation LR framework (Supporting <=0.48, Moderate <=0.23, Strong/Very Strong <=0.05/<=0.00285 per Appendix I), requiring evidence of non-segregation in affected family members. No pedigree, segregation, or non-segregation data for c.1387A>T is present in the case-evidence bundle.
Evidence considered
Case-evidence bundle contains no pedigree, family, or segregation data of any kind for NM_007294.4:c.1387A>T, so lack-of-segregation cannot be evaluated against the ENIGMA Appendix I quantitative method required for BS4.
Still missing
No pedigree or family segregation/non-segregation data available for this variant.
No quantitative co-segregation LR calculation exists to evaluate against ENIGMA BS4 thresholds.
BP1Not assessed: insufficient evidence was available to evaluate this criterion.
Details ▾Hide ▴
Reasoning
BP1 could not be assessed because its agent did not produce valid output.
Still missing
attempt 1: Hermes timed out after 200s and left no usable output_file
attempt 2: Hermes timed out after 200s and left no usable output_file
attempt 3: Hermes timed out after 200s and left no usable output_file
BP5Not assessed: no variant-specific clinical-history likelihood-ratio data were available.
Details ▾Hide ▴
Reasoning
ENIGMA v1.2 defines BP5 using the same Li et al. 2020 (PMID:31853058) clinical-history LR table used for PP4, with BP5 thresholds Supporting LR<=0.48, Moderate<=0.23, Strong<=0.05, Very Strong<=0.00285 (neutral zone 0.48-2.08 applies neither PP4 nor BP5). No exact-match row for NM_007294.4:c.1387A>T was found in the extracted clinical-history LR sheet content within this case's evidence bundle, so no LR value is available to evaluate BP5 in either direction.
Rule
BP5: combined clinical-history LR per ENIGMA BRCA1/2 Specifications v1.2 (Li et al. 2020, PMID:31853058) (cspec).
Evidence considered
ENIGMA BRCA1/2 Specifications v1.2 restricts BP5 to the same combined clinical-history LR model as PP4 (BP5 thresholds: Supporting LR<=0.48, Moderate<=0.23, Strong<=0.05, Very Strong<=0.00285), sourced from Li et al. 2020 (PMID:31853058) per the VCEP file index guidance.
The clinical_history_LR.xlsx extract present in this case's evidence bundle contains rows for other BRCA1 variants (e.g. c.197A>G, c.4986+3G>T) but no row matching NM_007294.4:c.1387A>T, so no LR value for this specific variant could be retrieved.
Still missing
No exact-match row for NM_007294.4:c.1387A>T was located in the Li 2020 (PMID:31853058) clinical-history LR table within the evidence bundle; a direct lookup against the source spreadsheet is needed before BP5 can be scored.
No case-level personal/family-history phenotype data for the individual(s) carrying this variant was supplied in the case bundle.
Not applicable · 12· recorded as not applicableShow reasons ▾Hide reasons ▴PS2VCEPNot applicable: BRCA1's expert panel excludes de novo evidence given the gene's reduced, age-dependent penetrance.
Details ▾Hide ▴
Reasoning
ClinGen ENIGMA BRCA1/BRCA2 Expert Panel Specification v1.2 explicitly marks PS2 as 'Not Applicable' for BRCA1/2 variant interpretation (autosomal dominant cancer predisposition genes with reduced/age-dependent penetrance are not amenable to the de novo confirmation model). The governing VCEP specification overrides generic ACMG PS2 usage for this gene.
Evidence considered
case_summary.json compact_evidence.cspec lists PS2 with applicability: 'Not Applicable' under the ENIGMA BRCA1/BRCA2 Expert Panel Specifications v1.2.
PS3N/ANot applicable: functional-assay evidence under this framework is restricted to missense and synonymous variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
NM_007294.4:c.1387A>T is a nonsense variant (NP_009225.1:p.(Lys463Ter)) predicted to trigger nonsense-mediated decay / premature truncation. The ENIGMA BRCA1/2 v1.2 specification restricts PS3/BS3 (functional-assay-based codes) to missense and synonymous variant types, evaluated via the calibrated Specifications Table 9 and Supplementary Table ST4 mammalian functional-assay datasets. Those tables were searched by HGVS coding change and contain no entry for c.1387A>T (entries checked include unrelated variants such as c.197A>G and c.4986+3G>T). For truncating/nonsense variants like this one, loss-of-function evidence is captured through the PVS1 pathway rather than PS3, per cspec. No case-specific in vitro or in vivo functional assay data for this exact PTC variant were identified in any source in the evidence bundle.
ENIGMA BRCA1/2 ACMG/AMP Specifications v1.2 (cspec): PS3 rule text specifies well-established in vitro/in vivo functional studies (protein-only or mRNA+protein combined) per Specifications Table 9 calibrated assay list, or mRNA-only assays applied via the PVS1(RNA) pathway.
Index guidance for Specifications_Table9_V1.2_2024-11-18.xlsx and SupplementaryTables_V1.2_2024-11-18.xlsx explicitly scope PS3/BS3 functional-assay code application to missense and synonymous variant types only.
case_summary.json normalization confirms NM_007294.4:c.1387A>T = NP_009225.1:p.(Lys463Ter), consequence_class 'nonsense' — a premature termination codon (PTC) variant, not missense/synonymous.
Supplementary Table ST4 (functional assay results dataset) rows checked contain no entry matching c.1387A>T; nearby rows found were for unrelated variants c.197A>G and c.4986+3G>T.
Still missing
No variant-specific functional assay (protein or mRNA) data located for c.1387A>T/p.(Lys463Ter) in ENIGMA Table 9 or Supplementary Table ST4.
PS3 is out of scope for this variant type under the ENIGMA v1.2 specification, which reserves PS3/BS3 for missense/synonymous variants.
PM4VCEPNot applicable: this criterion covers in-frame length changes, not a nonsense substitution like this one.
Details ▾Hide ▴
Reasoning
PM4 addresses protein length changes resulting from in-frame insertions/deletions or stop-loss variants in a non-repeat region. c.1387A>T is a nonsense substitution creating a premature stop (p.Lys463Ter), which truncates rather than alters the protein via an in-frame indel or loss of the native stop codon, so the PM4 mechanism does not apply to this variant type. The ENIGMA BRCA1/2 VCEP cspec explicitly marks PM4 as 'Not Applicable' as a specified criterion for this framework.
VCEP rule
PM4: Not Applicable per ENIGMA BRCA1/2 VCEP cspec; also mechanistically inapplicable to nonsense/stop-gain substitutions, which are evaluated under PVS1 rather than PM4.
Evidence considered
case_summary.json cspec block: entry {"label": "PM4", "applicability": "Not Applicable"} under the ENIGMA BRCA1/2 Expert Panel Specification v1.2 criteria list.
prefetch.json normalized protein consequence NP_009225.1:p.(Lys463Ter) confirms this is a nonsense (stop-gain) substitution, not an in-frame indel or stop-loss variant, which is the variant class PM4 is intended to evaluate.
PM6VCEPNot applicable: BRCA1's expert panel excludes assumed de novo evidence for this reduced-penetrance cancer gene.
Details ▾Hide ▴
Reasoning
ClinGen ENIGMA BRCA1/BRCA2 Expert Panel Specification v1.2 explicitly marks PM6 (assumed de novo without confirmed parentage) as 'Not Applicable' for this gene, consistent with the PS2 exclusion for reduced-penetrance adult-onset cancer predisposition.
Evidence considered
case_summary.json compact_evidence.cspec lists PM6 with applicability: 'Not Applicable' under the ENIGMA BRCA1/BRCA2 Expert Panel Specifications v1.2.
PP3N/ANot applicable: bioinformatic prediction criteria apply only to missense, silent, or intronic variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
NM_007294.4:c.1387A>T is a nonsense variant, NP_009225.1:p.(Lys463Ter), producing a premature termination codon rather than a missense, silent, or intronic change. The governing ENIGMA BRCA1/BRCA2 v1.2 specification scopes PP3's bioinformatic-prediction pathway explicitly to (a) missense/in-frame insertion-deletion-delins variants assessed via BayesDel no-AF score, or (b) silent, missense/in-frame, and intronic (outside donor/acceptor +/-1,2) variants assessed via SpliceAI for a splicing effect. Nonsense/PTC variants are not listed in either PP3 pathway; the loss-of-function mechanism for this variant class is instead captured under PVS1 (evaluated by a different group), and applying PP3 here would double-count that same predicted damaging mechanism. In addition, SpliceAI predicts no splice-altering effect at this position (max delta score = 0.001, far below the ENIGMA PP3 splicing threshold of >=0.2), so even under a splicing-path analysis no evidence supports PP3.
ENIGMA BRCA1/BRCA2 v1.2 specification (cSpec doc 1530970787): PP3 applies to missense/in-frame indel variants in a clinically important domain with BayesDel no-AF score >=0.28, OR to silent/missense/in-frame/intronic (outside +/-1,2) variants with SpliceAI >=0.2 delta score. Nonsense variants are excluded from this rule text.
SpliceAI Lookup result for NM_007294.4:c.1387A>T: max delta score = 0.001 (DS_AG 0.0, DS_AL 0.0, DS_DG 0.0, DS_DL 0.001), well below the 0.2 supporting-pathogenic threshold, so no splicing effect is predicted regardless of variant-type scoping.
A local BayesDel no-AF score (0.60222) is present in the source registry, but is not applied here because the variant is a nonsense/PTC change, which is outside the missense/in-frame scope of the ENIGMA PP3 protein-effect rule; applying it would inappropriately double-count the truncating (PVS1) mechanism.
Still missing
Variant type (nonsense/PTC) falls outside the ENIGMA-defined scope of the PP3 bioinformatic pathway; no applicable code exists for this variant class under this criterion.
PP5VCEPNot applicable: the variant is absent from ClinVar, so no expert-panel classification exists to invoke.
Details ▾Hide ▴
Reasoning
The ENIGMA BRCA1/2 Specifications v1.2 mark PP5 as 'Not Applicable' for this VCEP framework. Additionally, per the required exact-variant ClinVar expert-panel rule, PP5 can only trigger on an exact-variant 3-star/expert-panel ClinVar classification of Pathogenic/Likely pathogenic; the ClinVar search for NM_007294.4:c.1387A>T returned no result at all (variant absent from ClinVar), so there is no expert-panel record to invoke.
VCEP rule
PP5: Not Applicable per ENIGMA BRCA1/2 Specifications v1.2 (cspec); also no exact-variant ClinVar expert-panel record exists for this variant.
Evidence considered
ENIGMA BRCA1/2 Specifications v1.2 lists PP5 with applicability: Not Applicable for this VCEP.
ClinVar search for this exact variant returned no result (evidence_sentence: 'This variant is absent from ClinVar'), so no expert-panel classification is available to support PP5 regardless of VCEP applicability.
Still missing
Variant is absent from ClinVar entirely; no expert-panel classification exists to assess for PP5.
BS3N/ANot applicable: functional-assay evidence under this framework is restricted to missense and synonymous variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
For the same reason as PS3: c.1387A>T is a nonsense (PTC) variant, not a missense or synonymous variant, and the ENIGMA BRCA1/2 v1.2 specification's BS3 functional-assay pathway (Specifications Table 9 / Supplementary Table ST4) is scoped only to missense and synonymous types. No calibrated functional assay data for this variant were found in either table, and BS3 is not the applicable evidence pathway for a truncating variant of this kind under this VCEP framework.
ENIGMA BRCA1/2 ACMG/AMP Specifications v1.2 (cspec): BS3 rule text specifies well-established in vitro/in vivo functional studies showing no damaging effect (protein-only or mRNA+protein combined) per Specifications Table 9 calibrated assay list, or mRNA-only assays applied via BP7(RNA).
Index guidance for Specifications_Table9_V1.2_2024-11-18.xlsx and SupplementaryTables_V1.2_2024-11-18.xlsx explicitly scope PS3/BS3 functional-assay code application to missense and synonymous variant types only.
case_summary.json normalization confirms NM_007294.4:c.1387A>T = NP_009225.1:p.(Lys463Ter), consequence_class 'nonsense' — a premature termination codon (PTC) variant, not missense/synonymous.
BP2VCEPNot applicable: this criterion is excluded entirely under the BRCA1/BRCA2 expert-panel framework.
Details ▾Hide ▴
Reasoning
The ENIGMA BRCA1/2 v1.2 CSpec explicitly designates BP2 as 'Not Applicable' for BRCA1/BRCA2 variant classification (case_summary.json cspec.criteria, label BP2, applicability: Not Applicable). No generic ACMG fallback is used because a governing VCEP specification exists and explicitly addresses this criterion.
VCEP rule
ENIGMA BRCA1/2 v1.2 -- BP2 Not Applicable
Evidence considered
ENIGMA BRCA1/2 v1.2 CSpec (case_summary.json cspec.criteria) lists BP2 with applicability: 'Not Applicable', overriding generic ACMG BP2 (observed in trans with a pathogenic variant for a fully penetrant dominant disorder, or in cis with a pathogenic variant) for this gene
BP3VCEPNot applicable: this criterion covers in-frame indels in repetitive regions, not a nonsense substitution like this one.
Details ▾Hide ▴
Reasoning
BP3 addresses in-frame insertions/deletions in a repetitive region without a known clinically important function. c.1387A>T is a nonsense substitution (p.Lys463Ter), not an in-frame indel, so the BP3 mechanism does not apply. The ENIGMA BRCA1/2 VCEP cspec explicitly marks BP3 as 'Not Applicable' for BRCA1.
VCEP rule
BP3: Not Applicable per ENIGMA BRCA1/2 VCEP cspec; also mechanistically inapplicable to nonsense/stop-gain substitutions.
Evidence considered
case_summary.json cspec block: entry {"label": "BP3", "applicability": "Not Applicable"} under the ENIGMA BRCA1/2 Expert Panel Specification v1.2 criteria list.
prefetch.json normalized protein consequence NP_009225.1:p.(Lys463Ter) confirms this is a nonsense substitution, not an in-frame indel, which is the variant class BP3 is intended to evaluate.
BP4N/ANot applicable: computational benign-prediction criteria apply only to missense, silent, or intronic variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
The same variant-type scoping applies to BP4 as to PP3 under the ENIGMA BRCA1/BRCA2 v1.2 specification: the protein-effect pathway (BayesDel no-AF score <=0.15) is restricted to missense/in-frame insertion-deletion-delins variants, the silent-variant splicing pathway applies only to silent variants in a functional domain, and the intronic splicing pathway applies only to intronic variants outside the native donor/acceptor +/-1,2 positions. NM_007294.4:c.1387A>T, p.(Lys463Ter), is a nonsense (PTC-producing) exonic variant and does not fall into any of these categories, so BP4 is not applicable to this variant type regardless of the observed low SpliceAI score.
ENIGMA BRCA1/BRCA2 v1.2 specification (cSpec doc 1530970787): BP4 applies to missense/in-frame indel variants with BayesDel no-AF score <=0.15, silent variants in a functional domain with SpliceAI <=0.1, or intronic variants outside +/-1,2 with SpliceAI <=0.1. Nonsense variants are not covered by any BP4 rule branch.
SpliceAI Lookup result for NM_007294.4:c.1387A>T: max delta score = 0.001, which would be consistent with a benign splicing signal if BP4's splicing branches applied to this variant type, but they do not because the variant is exonic nonsense, not silent or intronic.
Still missing
Variant type (nonsense/PTC) falls outside the ENIGMA-defined scope of the BP4 bioinformatic pathway; no applicable code exists for this variant class under this criterion.
BP6VCEPNot applicable: the variant is absent from ClinVar, so no expert-panel benign classification exists to invoke.
Details ▾Hide ▴
Reasoning
The ENIGMA BRCA1/2 Specifications v1.2 mark BP6 as 'Not Applicable' for this VCEP framework. Per the required exact-variant ClinVar expert-panel rule, BP6 can only trigger on an exact-variant 3-star/expert-panel ClinVar classification of Benign/Likely benign; the ClinVar search for NM_007294.4:c.1387A>T returned no result (variant absent from ClinVar), so there is no expert-panel record to invoke, and this is also a nonsense/PTC variant with no benign signal in any consulted source.
VCEP rule
BP6: Not Applicable per ENIGMA BRCA1/2 Specifications v1.2 (cspec); also no exact-variant ClinVar expert-panel record exists for this variant.
Evidence considered
ENIGMA BRCA1/2 Specifications v1.2 lists BP6 with applicability: Not Applicable for this VCEP.
ClinVar search for this exact variant returned no result (evidence_sentence: 'This variant is absent from ClinVar'), so no expert-panel classification is available to support BP6 regardless of VCEP applicability.
Still missing
Variant is absent from ClinVar entirely; no expert-panel classification exists to assess for BP6.
BP7N/ANot applicable: this criterion covers silent or intronic variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
BP7 under the ENIGMA BRCA1/BRCA2 v1.2 specification applies only to intronic and silent (synonymous) variants (and, for the RNA-based strong tier, also missense/in-frame variants outside a functional domain with a well-established negative functional mRNA assay). NM_007294.4:c.1387A>T results in p.(Lys463Ter), a nonsense/premature-termination-codon variant, not a synonymous or intronic change, and no BS3-level mRNA functional assay evidence negating splicing impact is present in this case's evidence bundle. BP7 is therefore not applicable to this variant.
ENIGMA BRCA1/BRCA2 v1.2 specification (cSpec doc 1530970787): BP7 rules are restricted to intronic variants, silent (synonymous) variants, and missense/in-frame variants outside a clinically important domain with a qualifying negative mRNA functional assay (BS3). None of these categories match a nonsense variant.
Still missing
Variant is nonsense (not synonymous/intronic), which is outside the ENIGMA-defined scope of BP7.
Every interpreted variant in BRCA1, mapped onto the exon structure of NM_007294.4. Select a row to find it on the plot.
BRCA1NM_007294.4
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in BRCA1—Select a row to find it on the plot; use the link to open its page.
Protein
Location
Classification
Link
gnomAD v4.1Allele count data not recorded
gnomAD v2.1Allele count data not recorded
gnomAD-Canada v1.0Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
SpliceAI acceptor lossat +107 bp
0.000
SpliceAI acceptor gainat -64 bp
0.000
SpliceAI donor lossat -288 bp
0.001
SpliceAI donor gainat +133 bp
0.000
Pangolin splice lossmagnitude shown
-0.006
Pangolin splice gain
0.017
Other predictors
REVEL
Not available
BayesDel
0.602
How the predictions were used
PP3N/ANot applicable: bioinformatic prediction criteria apply only to missense, silent, or intronic variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
NM_007294.4:c.1387A>T is a nonsense variant, NP_009225.1:p.(Lys463Ter), producing a premature termination codon rather than a missense, silent, or intronic change. The governing ENIGMA BRCA1/BRCA2 v1.2 specification scopes PP3's bioinformatic-prediction pathway explicitly to (a) missense/in-frame insertion-deletion-delins variants assessed via BayesDel no-AF score, or (b) silent, missense/in-frame, and intronic (outside donor/acceptor +/-1,2) variants assessed via SpliceAI for a splicing effect. Nonsense/PTC variants are not listed in either PP3 pathway; the loss-of-function mechanism for this variant class is instead captured under PVS1 (evaluated by a different group), and applying PP3 here would double-count that same predicted damaging mechanism. In addition, SpliceAI predicts no splice-altering effect at this position (max delta score = 0.001, far below the ENIGMA PP3 splicing threshold of >=0.2), so even under a splicing-path analysis no evidence supports PP3.
ENIGMA BRCA1/BRCA2 v1.2 specification (cSpec doc 1530970787): PP3 applies to missense/in-frame indel variants in a clinically important domain with BayesDel no-AF score >=0.28, OR to silent/missense/in-frame/intronic (outside +/-1,2) variants with SpliceAI >=0.2 delta score. Nonsense variants are excluded from this rule text.
SpliceAI Lookup result for NM_007294.4:c.1387A>T: max delta score = 0.001 (DS_AG 0.0, DS_AL 0.0, DS_DG 0.0, DS_DL 0.001), well below the 0.2 supporting-pathogenic threshold, so no splicing effect is predicted regardless of variant-type scoping.
A local BayesDel no-AF score (0.60222) is present in the source registry, but is not applied here because the variant is a nonsense/PTC change, which is outside the missense/in-frame scope of the ENIGMA PP3 protein-effect rule; applying it would inappropriately double-count the truncating (PVS1) mechanism.
Still missing
Variant type (nonsense/PTC) falls outside the ENIGMA-defined scope of the PP3 bioinformatic pathway; no applicable code exists for this variant class under this criterion.
BP4N/ANot applicable: computational benign-prediction criteria apply only to missense, silent, or intronic variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
The same variant-type scoping applies to BP4 as to PP3 under the ENIGMA BRCA1/BRCA2 v1.2 specification: the protein-effect pathway (BayesDel no-AF score <=0.15) is restricted to missense/in-frame insertion-deletion-delins variants, the silent-variant splicing pathway applies only to silent variants in a functional domain, and the intronic splicing pathway applies only to intronic variants outside the native donor/acceptor +/-1,2 positions. NM_007294.4:c.1387A>T, p.(Lys463Ter), is a nonsense (PTC-producing) exonic variant and does not fall into any of these categories, so BP4 is not applicable to this variant type regardless of the observed low SpliceAI score.
ENIGMA BRCA1/BRCA2 v1.2 specification (cSpec doc 1530970787): BP4 applies to missense/in-frame indel variants with BayesDel no-AF score <=0.15, silent variants in a functional domain with SpliceAI <=0.1, or intronic variants outside +/-1,2 with SpliceAI <=0.1. Nonsense variants are not covered by any BP4 rule branch.
SpliceAI Lookup result for NM_007294.4:c.1387A>T: max delta score = 0.001, which would be consistent with a benign splicing signal if BP4's splicing branches applied to this variant type, but they do not because the variant is exonic nonsense, not silent or intronic.
Still missing
Variant type (nonsense/PTC) falls outside the ENIGMA-defined scope of the BP4 bioinformatic pathway; no applicable code exists for this variant class under this criterion.
BP7N/ANot applicable: this criterion covers silent or intronic variants, not this nonsense change.
Details ▾Hide ▴
Reasoning
BP7 under the ENIGMA BRCA1/BRCA2 v1.2 specification applies only to intronic and silent (synonymous) variants (and, for the RNA-based strong tier, also missense/in-frame variants outside a functional domain with a well-established negative functional mRNA assay). NM_007294.4:c.1387A>T results in p.(Lys463Ter), a nonsense/premature-termination-codon variant, not a synonymous or intronic change, and no BS3-level mRNA functional assay evidence negating splicing impact is present in this case's evidence bundle. BP7 is therefore not applicable to this variant.
ENIGMA BRCA1/BRCA2 v1.2 specification (cSpec doc 1530970787): BP7 rules are restricted to intronic variants, silent (synonymous) variants, and missense/in-frame variants outside a clinically important domain with a qualifying negative mRNA functional assay (BS3). None of these categories match a nonsense variant.
Still missing
Variant is nonsense (not synonymous/intronic), which is outside the ENIGMA-defined scope of BP7.
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). BayesDel score = 0.60222.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
Tumorigenesis in mice carrying a truncating Brca1 mutation.
Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.
This variant was interpreted by pipeline 7.2.0.
The current version is 11.0.07.
Re-running queues a fresh interpretation; the result replaces this page when complete.
Re-runs are not free. Blank draws on today's public interpretation allowance; with a code, it uses one of that code's uses.