About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.3881T>G, p.(Leu1294Ter)
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A 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.
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 BRCA2 VCEP v1.2.0. 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.
Pathogenic evidence criteria: 4
Benign evidence criteria: 0
Pathogenic criteria applied · 4
PVS1Very strong
PVS1 · very strong
Nonsense variant NM_000059.3:c.3881T>G (p.Leu1294Ter) in BRCA2 exon 11 introduces a premature termination codon predicted to truncate the protein at residue 1294 of 3418, removing the C-terminal DNA-binding domain (aa 2481-3186) and nuclear localization signals. Loss of function is the established disease mechanism for BRCA2. Per ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PVS1 (Very Strong). No predicted or observed rescue via alternative splicing (SpliceAI max delta = 0.00).
PM2Supporting
PM2 · supporting
Variant is absent from gnomAD v2.1 (exome), gnomAD v4.1, and gnomAD-Canada v1.0. Per ENIGMA PM2 rule, absence from controls in outbred populations supports PM2_Supporting. gnomAD v2.1/v4.1 returned null allele counts consistent with absence from the database. gnomAD-Canada confirms zero allele observations.
PM5Strong
PM5 · strong
Per ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PM5_Strong (PTC). Exon 11 is not among the PM5_N/A exons (E12, E27, E6), and numerous proven pathogenic PTC variants have been reported in this exon. This provides additional weight beyond PVS1 for the protein termination codon.
PP5Supporting
PP5 · supporting
Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) classified as Pathogenic.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
ENIGMA BRCA1/BRCA2 Specification v1.2.0 Table 3 combining rules applied to adjudicated criteria. PVS1 (Very Strong) + PM5_Strong exceeds the Pathogenic threshold (1 Very Strong + 1 Strong). Additionally, PVS1 + PM2_Supporting + PP5_Supporting independently satisfies 1 Very Strong + 2 Supporting → Pathogenic. No benign criteria met; no conflicting evidence.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
No screenshot for this evidence
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
7 Pathogenic.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA2 VCEP v1.2.0, with the data and sources behind each one.
27 criteria with recorded statuses: 4 met · 3 not met · 8 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000059.3:c.3881T>G (p.Leu1294Ter) is a nonsense variant in BRCA2 exon 11 that introduces a premature termination codon at residue 1294 of 3418, predicted to result in loss of the C-terminal DNA-binding domain and nuclear localization signals.
PVS1 (Very Strong) is met per ENIGMA Specifications Table 4, which assigns PVS1 to BRCA2 exon 11 PTC variants. Loss of function is the established disease mechanism for BRCA2.
PM5_Strong (PTC) is met per ENIGMA Table 4, which assigns PM5_Strong (PTC) for BRCA2 exon 11 termination codon variants. Exon 11 harbors numerous proven pathogenic PTC variants.
PM2_Supporting is met: the variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0, consistent with a rare pathogenic variant in outbred populations.
The variant has been classified as Pathogenic by the ENIGMA expert panel and 7 clinical laboratories in ClinVar (VariationID: 266780).
Under ENIGMA Table 3 combining rules, PVS1 (Very Strong) + PM5_Strong + PM2_Supporting meets the criteria for Pathogenic classification (1 Very Strong + 1 Strong fulfills the Pathogenic threshold).
No criteria match.
Met · 4
PVS1 Very strongNonsense variant NM_000059.3:c.3881T>G (p.Leu1294Ter) in BRCA2 exon 11 introduces a premature termination codon predicted to truncate the protein at residue 1294 of 3418, removing the C-terminal DNA-binding domain (aa 2481-3186) and nuclear localization signals. Loss of function is the established disease mechanism for BRCA2. Per ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PVS1 (Very Strong). No predicted or observed rescue via alternative splicing (SpliceAI max delta = 0.00). Details ▾Hide ▴
Evidence considered
- Nonsense variant p.Leu1294Ter in BRCA2 exon 11
- ENIGMA Table 4 assigns PVS1 (Very Strong) for BRCA2 exon 11 PTC variants
- SpliceAI max delta score 0.00 — no predicted splice alteration
- LOF established disease mechanism per CSPEC PVS1 guidance
Sources
PM2 SupportingVariant is absent from gnomAD v2.1 (exome), gnomAD v4.1, and gnomAD-Canada v1.0. Per ENIGMA PM2 rule, absence from controls in outbred populations supports PM2_Supporting. gnomAD v2.1/v4.1 returned null allele counts consistent with absence from the database. gnomAD-Canada confirms zero allele observations. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 exome (non-cancer subset)
- Absent from gnomAD v4.1
- Absent from gnomAD-Canada v1.0 (AC=0
- AN=0)
Still missing
- gnomAD v2.1 and v4.1 returned null allele counts rather than explicit zero
- verify read depth ≥25 at the variant position per ENIGMA Appendix G
Sources
PM5 StrongPer ENIGMA Specifications Table 4, BRCA2 exon 11 PTC variants are assigned PM5_Strong (PTC). Exon 11 is not among the PM5_N/A exons (E12, E27, E6), and numerous proven pathogenic PTC variants have been reported in this exon. This provides additional weight beyond PVS1 for the protein termination codon. Details ▾Hide ▴
Evidence considered
- ENIGMA Table 4 assigns PM5_Strong (PTC) for BRCA2 exon 11
- Exon 11 is within the PM5_PTC-applicable exon set
- Multiple proven pathogenic PTC variants reported in BRCA2 exon 11
Sources
Not met · 3 · evaluated, threshold not reached
PP3 ENIGMA PP3 applies to: (a) missense/in-frame variants inside a clinically important functional domain with BayesDel no-AF score ≥ 0.30, or (b) variants with predicted splicing impact (SpliceAI ≥ 0.2). This variant is a nonsense change, not a missense. SpliceAI max delta score is 0.00, indicating no predicted splicing impact. Neither condition for PP3 is met. Details ▾Hide ▴
Evidence considered
- Nonsense variant — not eligible for missense-based PP3
- SpliceAI max delta 0.00 — below PP3 splicing threshold of 0.2
- BayesDel no-AF score 0.058 — below PP3 threshold of 0.30
- though not applicable to nonsense variant
Sources
BA1 Variant is absent from gnomAD. ENIGMA BA1 requires filter allele frequency (FAF) above 0.1% (FAF > 0.001) in gnomAD non-founder populations. The variant does not meet this threshold. Details ▾Hide ▴
Evidence considered
- Variant absent from gnomAD — no population frequency data to support BA1
Sources
BS1 Variant is absent from gnomAD. ENIGMA BS1 requires FAF above 0.002% (BS1_Supporting) or above 0.01% (BS1). The variant does not meet either threshold. Details ▾Hide ▴
Evidence considered
- Variant absent from gnomAD — frequency too low for BS1
Sources
Not assessed · 8 · no assessment recorded
PS3 No variant-specific functional assay data available for NM_000059.3:c.3881T>G. ENIGMA Specifications Table 9 (calibrated functional assay results) does not list this variant. Five full-text papers were reviewed (PMID:10570174, PMID:22193408, PMID:24312913, PMID:20104584, PMID:25741868) and none reported functional data for this specific variant. OncoKB classifies the variant as 'Likely Oncogenic' with a 'Likely Loss-of-function' biological effect based on curated literature, but this is a somatic annotation and does not constitute calibrated germline PS3 evidence. Details ▾Hide ▴
Evidence considered
- Variant not listed in ENIGMA Table 9 (calibrated functional assays)
- OncoKB: Likely Oncogenic
- Likely Loss-of-function (somatic context
- not germline PS3)
Still missing
- No calibrated germline functional assay data for this variant
- OncoKB somatic annotation may support biological plausibility but does not meet ENIGMA PS3 threshold
Sources
vcep_specifications_table9_v1_2_2024_11_18oncokb ↗
PS4 No case-control study data with odds ratios available for this specific variant. ENIGMA PS4 requires case-control studies with p ≤ 0.05 and OR ≥ 4 (lower CI excludes 2.0). The variant has been reported in ClinVar as Pathogenic by 7 clinical laboratories and by the ENIGMA expert panel, suggesting it has been observed in affected individuals, but quantitative case-control data are not available for formal PS4 application. Details ▾Hide ▴
Evidence considered
- ClinVar: Pathogenic
- reviewed by expert panel (ENIGMA)
- 7 clinical laboratory submissions
- No case-control OR data available for PS4 quantification
Still missing
- No formal case-control study with OR for this variant
- ClinVar submission count suggests observation in affected individuals but does not meet ENIGMA PS4 threshold alone
Sources
PP1 No cosegregation data available for this variant. ENIGMA PP1 requires quantitative cosegregation analysis with LR ≥ 2.08 (Supporting), ≥ 4.3 (Moderate), or ≥ 18.7 (Strong). No cosegregation LR data were found in the reviewed evidence sources. Details ▾Hide ▴
Evidence considered
- No cosegregation LR data available for this variant
Still missing
- No family cosegregation data identified in any reviewed source
Sources
PP4 No clinical history likelihood ratio data available for this variant. ENIGMA PP4 requires combined LR ≥ 2.08 (Supporting), ≥ 4.3 (Moderate), or ≥ 18.7 (Strong) from multifactorial likelihood clinical data. The variant was not found in the Li et al. 2020 (PMID:31853058) BRCA2 clinical history LR table. The variant was not found in the Parsons et al. 2019 (HUMU-40-1557-s001) multifactorial analysis table (which primarily covers missense and splicing variants). Details ▾Hide ▴
Evidence considered
- Variant not listed in Li et al. 2020 BRCA2 clinical history LR table
- Variant not listed in Parsons et al. 2019 multifactorial analysis (HUMU SuppT1)
Still missing
- No clinical history LR data for this specific variant
- ENIGMA PP4/BP5 multifactorial data not available for this nonsense variant in the standard lookup tables
Sources
vcep_pmid_31853058_brca2_clinical_history_lrvcep_humu_40_1557_s001
BS2 No proband-level data with Fanconi anemia phenotype assessment available. ENIGMA BS2 requires evaluation of probands for absence of recessive Fanconi Anemia features, with point-based assignment per Specifications Table 8. No individual-level clinical data were available for review. Details ▾Hide ▴
Evidence considered
- No proband-level phenotype data available for BS2 assessment
Still missing
- Individual-level clinical phenotype data needed for BS2 point assignment per ENIGMA Table 8
Sources
BS3 No variant-specific functional assay data showing no damaging effect. ENIGMA Specifications Table 9 (calibrated functional assay results for PS3/BS3) does not list this variant. Five full-text papers were reviewed (PMID:10570174, PMID:22193408, PMID:24312913, PMID:20104584, PMID:25741868) and none reported benign functional data for this specific variant. Details ▾Hide ▴
Evidence considered
- Variant not listed in ENIGMA Table 9
- No benign functional assay data identified in reviewed literature
Still missing
- No calibrated functional assay data showing no damaging effect for this variant
Sources
vcep_specifications_table9_v1_2_2024_11_18
BS4 No cosegregation data available. ENIGMA BS4 requires quantitative lack-of-segregation analysis with LR ≤ 0.48 (Supporting), ≤ 0.23 (Moderate), or ≤ 0.05 (Strong). No segregation LR data were found for this variant. Details ▾Hide ▴
Evidence considered
- No segregation LR data available for this variant
Still missing
- No lack-of-segregation data identified
Sources
BP5 No multifactorial likelihood data supporting benignity available for this variant. ENIGMA BP5 requires combined LR ≤ 0.48 (Supporting), ≤ 0.23 (Moderate), or ≤ 0.05 (Strong). The variant was not found in the Li et al. 2020 (PMID:31853058) BRCA2 clinical history LR table or the Parsons et al. 2019 multifactorial analysis. Details ▾Hide ▴
Evidence considered
- Variant not listed in Li et al. 2020 BRCA2 clinical history LR table
- Variant not listed in Parsons et al. 2019 multifactorial analysis
Still missing
- No multifactorial LR data supporting benignity for this variant
Sources
vcep_pmid_31853058_brca2_clinical_history_lrvcep_humu_40_1557_s001
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 under ENIGMA applies to missense substitutions with a previously classified pathogenic variant at the same residue, or to exonic/intronic variants with the same predicted splicing impact as a known pathogenic variant. This variant is a nonsense (PTC) change, not a missense substitution, and SpliceAI shows no splicing impact (max delta = 0.00). PS1 rules do not apply. Details ▾Hide ▴
Evidence considered
- Nonsense variant — not a missense substitution eligible for PS1
- SpliceAI max delta 0.00 — no predicted splicing impact that could support PS1 via splicing mechanism
Sources
PS2 VCEPENIGMA BRCA2 VCEP v1.2 marks PS2 as not applicable. Details ▾Hide ▴
PM1 VCEPPM1 is not applicable under ENIGMA BRCA2 VCEP v1.2. Per CSPEC rules, PM1 is considered a component of bioinformatic analysis (PP3/BP4) rather than an independent criterion. Details ▾Hide ▴
Evidence considered
- ENIGMA VCEP specifies PM1 as not applicable — subsumed under PP3/BP4 bioinformatic analysis
Sources
PM6 VCEPENIGMA BRCA2 VCEP v1.2 marks PM6 as not applicable. Details ▾Hide ▴
PP2 VCEPENIGMA BRCA2 VCEP v1.2 marks PP2 as not applicable. Details ▾Hide ▴
BP1 N/AENIGMA BP1 applies to silent, missense, or in-frame insertion/deletion/delins variants outside a clinically important functional domain with no splicing predicted. This variant is a nonsense change and does not fall within the scope of BP1. Details ▾Hide ▴
Evidence considered
- Nonsense variant — BP1 applies only to silent
- missense
- or in-frame variants
Sources
BP2 VCEPENIGMA BRCA2 VCEP v1.2 marks BP2 as not applicable. Details ▾Hide ▴
BP3 VCEPTrivially not applicable — in-frame deletions/insertions in repetitive regions without known function. This is a single-nucleotide nonsense substitution. Details ▾Hide ▴
No further detail was recorded.
BP4 N/AENIGMA BP4 applies to missense/in-frame variants inside a clinically important functional domain with no predicted impact (BayesDel ≤ 0.18 AND SpliceAI ≤ 0.1), or to silent/intronic variants with no splicing impact. This variant is a nonsense change and is not eligible for BP4 under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Nonsense variant — BP4 applies only to missense
- silent
- in-frame
- or intronic variants per ENIGMA Figure 1A
Sources
BP6 VCEPENIGMA BRCA2 VCEP v1.2 marks BP6 as not applicable. Details ▾Hide ▴
BP7 N/AENIGMA BP7 applies to silent/intronic/missense variants with mRNA assay evidence of no splicing impact, or to silent variants inside clinically important domains if BP4 is met. This variant is a nonsense change and is not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Nonsense variant — BP7 applies only to silent
- intronic
- or missense variants per ENIGMA Figure 1A/1B
Sources
PS5 N/APS5 is not included in the assess list for this adjudication. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.3
- Coding (HGVS c.)
- NM_000059.3:c.3881T>G
- Protein (HGVS p.)
- NP_000050.2:p.(Leu1294Ter)
- GRCh38
- chr13:32338236 T>G
- GRCh37
- chr13:32912373 T>G
- ClinVar
- 266780
Gene diagram
Every interpreted variant in BRCA2, mapped onto the exon structure of NM_000059.3. Select a row to find it on the plot.
BRCA2NM_000059.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in BRCA2
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- 0.058
How the predictions were used
PP3 ENIGMA PP3 applies to: (a) missense/in-frame variants inside a clinically important functional domain with BayesDel no-AF score ≥ 0.30, or (b) variants with predicted splicing impact (SpliceAI ≥ 0.2). This variant is a nonsense change, not a missense. SpliceAI max delta score is 0.00, indicating no predicted splicing impact. Neither condition for PP3 is met. Details ▾Hide ▴
Evidence considered
- Nonsense variant — not eligible for missense-based PP3
- SpliceAI max delta 0.00 — below PP3 splicing threshold of 0.2
- BayesDel no-AF score 0.058 — below PP3 threshold of 0.30
- though not applicable to nonsense variant
Sources
BP4 N/AENIGMA BP4 applies to missense/in-frame variants inside a clinically important functional domain with no predicted impact (BayesDel ≤ 0.18 AND SpliceAI ≤ 0.1), or to silent/intronic variants with no splicing impact. This variant is a nonsense change and is not eligible for BP4 under ENIGMA rules. Details ▾Hide ▴
Evidence considered
- Nonsense variant — BP4 applies only to missense
- silent
- in-frame
- or intronic variants per ENIGMA Figure 1A
Sources
BP7 N/AENIGMA BP7 applies to silent/intronic/missense variants with mRNA assay evidence of no splicing impact, or to silent variants inside clinically important domains if BP4 is met. This variant is a nonsense change and is not eligible for BP7. Details ▾Hide ▴
Evidence considered
- Nonsense variant — BP7 applies only to silent
- intronic
- or missense variants per ENIGMA Figure 1A/1B
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). BayesDel score = 0.0577565.
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
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PMID 10570174 ↗Truncated BRCA2 is cytoplasmic: implications for cancer-linked mutations.Spain et al. demonstrate that truncated BRCA2 protein products are cytoplasmic rather than nuclear, providing a mechanistic basis for pathogenicity of C-terminal truncating mutations. NM_000059.3:c.3881T>G was not specifically identified in this paper.Does not name this variant
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PMID 11239455 ↗BRCA2 is required for homology-directed repair of chromosomal breaks.Moynahan et al. demonstrate that BRCA2 is required for homology-directed repair of chromosomal breaks using cell lines with engineered BRCA2 mutations. NM_000059.3:c.3881T>G was not specifically studied in this paper.Does not name this variant
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PMID 20878484 ↗A new mutation of BRCA2 gene in an Italian healthy woman with familial breast cancer history.Reports a new BRCA2 mutation in an Italian healthy woman with familial breast cancer history. NM_000059.3:c.3881T>G was not identified in this paper.Does not name this variant
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PMID 22193408 ↗BRCA1 and BRCA2: different roles in a common pathway of genome protection.Roy et al. review the distinct roles of BRCA1 and BRCA2 in genome protection pathways. NM_000059.3:c.3881T>G was not specifically identified in this review.Does not name this variant
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PMID 24312913 ↗A comprehensive focus on global spectrum of BRCA1 and BRCA2 mutations in breast cancer.Karami and Mehdipour provide a comprehensive review of global BRCA1 and BRCA2 mutation spectra across populations. NM_000059.3:c.3881T>G was not specifically catalogued in this review.Does not name this variant
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PMID 20104584 ↗Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.Borg A et al. · 2010Borg et al. characterize BRCA1 and BRCA2 deleterious mutations and VUS in the WECARE study of contralateral and unilateral breast cancer. NM_000059.3:c.3881T>G was not identified among the 470 unique sequence variants reported in this study.Does not name this variant
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards et al. present the ACMG/AMP standards and guidelines for sequence variant interpretation. This is a methodological guideline paper and does not report on specific variants.Does not name this variant
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PMID 28039656 ↗Novel and reported pathogenic variants in exon 11 of BRCA2 gene in a cohort of Sri Lankan young breast cancer patients.De Silva S et al. · 2017De Silva et al. report novel and reported pathogenic variants in exon 11 of BRCA2 in a cohort of Sri Lankan young breast cancer patients. This paper is cited by multiple ClinVar submissions for NM_000059.3:c.3881T>G and likely reports the variant, but full text was not available for confirmation.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
7 Pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535438831
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/266780/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32912373-T-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32338236-T-G?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/13-32338236-T-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.3%3Ac.3881…
- OncoKB ↗www.oncokb.org/gene/BRCA2/L1294*
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.3881T%3EG
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (7 clinical laboratories) and as Pathogenic by Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) (expert panel). (ClinVarID = 266780)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). BayesDel score = 0.0577565.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.