About BRCA1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA1 c.68_69del, p.(Glu23ValfsTer17)
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 BRCA1 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: 5
Benign evidence criteria: 1
Pathogenic criteria applied · 5
PVS1Very strong
PVS1 · very strong
This variant is a frameshift deletion in BRCA1 exon 2, predicted to cause p.(Glu23ValfsTer17). BRCA1 loss of function is an established disease mechanism, and ENIGMA Table 4 designates exon 2 protein-truncating variants for full-strength PVS1, so this evidence supports PVS1 at Very Strong strength.
PS3Strong
PS3 · strong
This variant is listed in ENIGMA Table 9 as PS3 Strong based on a calibrated functional study that showed protein function similar to pathogenic control variants. This is consistent with OncoKB describing the variant as an oncogenic loss-of-function alteration.
PM5Strong
PM5 · strong
This frameshift creates a premature termination codon in BRCA1 exon 2. ENIGMA Table 4 designates exon 2 protein-truncating variants for PM5_Strong (PTC), so this variant meets PM5 at Strong strength.
PP4Very strong
PP4 · very strong
This variant has a BRCA1 clinical-history likelihood ratio of 1.145935772193482e+20 from 202 probands in the BRCA1 clinical-history dataset. This value is far above the ENIGMA PP4_Very Strong threshold of 350, so the clinical-history evidence strongly supports pathogenicity.
PP5Supporting
PP5 · supporting
Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Pathogenic.
Benign criteria applied · 1
BS1Supporting
BS1 · supporting
This variant is present above the ENIGMA BS1_Supporting population threshold but below the BS1 threshold. The gnomAD v2.1 filter allele frequency is 5.395e-05 and the gnomAD v4.1 filter allele frequency is 2.478e-05, which are above 0.00002 and below or equal to 0.0001, consistent with BS1 at Supporting strength.
Recorded classification: Pathogenic
ENIGMA BRCA1 and BRCA2 Specification v1.2 Table 3 conflicting-evidence point system; pathogenic evidence totals 25 points (PVS1_Very Strong, PS3_Strong, PM5_Strong, PP4_Very Strong, PP5_Supporting) and benign evidence totals -1 point (BS1_Supporting), for a net score of 24.
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
191 / 1,612,084 alleles
gnomAD v4.1: 191 / 1,612,084 alleles. Recorded AF 0.00011848. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000205352; MAF= 0.02054%, 58/282442 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00405093; MAF= 0.40509%, 42/10368 alleles, homozygotes = 0); grpmax FAF= 5.395e-05.
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Functional evidence
Statement recorded
OncoKB classifies this variant as Oncogenic; biological effect: Loss-of-function.
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA1 VCEP v1.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 6 met · 4 not met · 5 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRCA1 c.68_69del (p.Glu23ValfsTer17; p.E23Vfs*17) variant is reported in ClinVar as Pathogenic, including expert-panel classification by ClinGen ENIGMA, and is also described by OncoKB as an oncogenic loss-of-function alteration.
This variant is present in population databases, with gnomAD v2.1 AF 0.000205352 (58/282442 alleles) and gnomAD v4.1 AF 0.00011848 (191/1612084 alleles); the observed filter allele frequencies of 5.395e-05 in v2.1 and 2.478e-05 in v4.1 are below the BA1 threshold of 0.001 but within the ENIGMA BS1_Supporting range above 0.00002 and less than or equal to 0.0001.
ENIGMA functional data assign PS3 Strong to this variant, with calibrated assay evidence showing a damaging effect consistent with a deleterious control profile.
SpliceAI predicts no significant splice impact for this variant, with a maximum delta score of 0.00, which is consistent with the primary effect being protein truncation rather than splice disruption.
This early exon 2 frameshift introduces a premature termination codon at p.Glu23ValfsTer17, and ENIGMA exon-level rules support PVS1 at Very Strong strength and PM5 for protein-truncating variants in this exon.
No criteria match.
Met · 6
PVS1 Very strongThis variant is a frameshift deletion in BRCA1 exon 2, predicted to cause p.(Glu23ValfsTer17). BRCA1 loss of function is an established disease mechanism, and ENIGMA Table 4 designates exon 2 protein-truncating variants for full-strength PVS1, so this evidence supports PVS1 at Very Strong strength. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification PVS1 for null variants, using Table 4 exon-level weighting.
Evidence considered
- NM_007294.4:c.68_69del is predicted as NP_009225.1:p.(Glu23ValfsTer17)
- Variant Validator places the change in exon 2
- BRCA1 PVS1 gene gate is eligible
- ENIGMA Table 4 lists BRCA1 exon 2 PTC variants as PVS1
Sources
PS3 StrongThis variant is listed in ENIGMA Table 9 as PS3 Strong based on a calibrated functional study that showed protein function similar to pathogenic control variants. This is consistent with OncoKB describing the variant as an oncogenic loss-of-function alteration. Details ▾Hide ▴
Rule
ENIGMA PS3 from calibrated functional studies, with variant-specific assignment in Table 9.
Evidence considered
- ENIGMA Table 9 entry: BRCA1 c.68_69del p.(Glu23Valfs*17) PS3 Strong
- Supplementary Table 4: Functional impact - complete
- Deleterious-control
- OncoKB classification: Oncogenic
- biological effect: Loss-of-function
Sources
PM5 StrongThis frameshift creates a premature termination codon in BRCA1 exon 2. ENIGMA Table 4 designates exon 2 protein-truncating variants for PM5_Strong (PTC), so this variant meets PM5 at Strong strength. Details ▾Hide ▴
Rule
ENIGMA PM5 for protein-terminating variants uses exon-specific PTC weighting from Table 4.
Evidence considered
- Variant is a protein-truncating frameshift in exon 2
- ENIGMA Table 4 exon 2 PTC row: PM5_Strong (PTC)
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PP4 Very strongThis variant has a BRCA1 clinical-history likelihood ratio of 1.145935772193482e+20 from 202 probands in the BRCA1 clinical-history dataset. This value is far above the ENIGMA PP4_Very Strong threshold of 350, so the clinical-history evidence strongly supports pathogenicity. Details ▾Hide ▴
Rule
ENIGMA PP4 uses calibrated multifactorial clinical-history likelihood ratios.
Evidence considered
- HGVS_Nucleotide c.68_69delAG
- N_Probands = 202
- LR = 1.145935772193482e+20
- ENIGMA PP4_Very Strong threshold = 350
Sources
PP5 SupportingExpert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Pathogenic. Details ▾Hide ▴
BS1 SupportingThis variant is present above the ENIGMA BS1_Supporting population threshold but below the BS1 threshold. The gnomAD v2.1 filter allele frequency is 5.395e-05 and the gnomAD v4.1 filter allele frequency is 2.478e-05, which are above 0.00002 and below or equal to 0.0001, consistent with BS1 at Supporting strength. Details ▾Hide ▴
Rule
ENIGMA BS1 uses filter allele frequency thresholds in non-founder populations.
Evidence considered
- gnomAD v2.1 grpmax FAF = 5.395e-05
- gnomAD v4.1 grpmax FAF = 2.478e-05
- ENIGMA BS1_Supporting threshold > 0.00002 and <= 0.0001
Sources
Not met · 4 · evaluated, threshold not reached
PM2 This variant is not absent from population databases. It is present in gnomAD v2.1 at AF 0.000205352 (58/282442 alleles) and in gnomAD v4.1 at AF 0.00011848 (191/1612084 alleles), so the ENIGMA requirement for absence from controls for PM2_Supporting is not met. Details ▾Hide ▴
Rule
ENIGMA PM2_Supporting requires absence from controls in gnomAD.
Evidence considered
- gnomAD v2.1 total AF 0.000205352
- 58/282442 alleles
- 0 homozygotes
- gnomAD v4.1 total AF 0.00011848
- 191/1612084 alleles
Sources
BA1 Available population data do not meet the BA1 threshold. The observed gnomAD filter allele frequencies are 5.395e-05 in v2.1 and 2.478e-05 in v4.1, both below the ENIGMA BA1 threshold of 0.001. Details ▾Hide ▴
Rule
ENIGMA BA1 requires FAF greater than 0.001 in a non-founder population.
Evidence considered
- gnomAD v2.1 grpmax FAF = 5.395e-05
- gnomAD v4.1 grpmax FAF = 2.478e-05
- ENIGMA BA1 threshold = 0.001
Sources
BS3 Available functional evidence does not support a benign effect. Instead, ENIGMA Table 9 assigns this variant PS3 Strong for a damaging functional result, so BS3 is not met. Details ▾Hide ▴
Rule
ENIGMA BS3 requires well-established studies showing no damaging effect.
Evidence considered
- ENIGMA Table 9 assigns PS3 Strong
- Supplementary Table 4 describes complete functional impact
Sources
vcep_specifications_table9_v1_2_2024_11_18vcep_supplementarytables_v1_2_2024_11_18
BP5 The BRCA1 clinical-history likelihood ratio for this variant is 1.145935772193482e+20 from 202 probands, which is far above the benign BP5 thresholds and strongly favors pathogenicity. BP5 is therefore not met. Details ▾Hide ▴
Rule
ENIGMA BP5 uses multifactorial clinical-history likelihood ratios in the benign direction.
Evidence considered
- LR = 1.145935772193482e+20
- N_Probands = 202
- BP5 benign threshold <= 0.48
Sources
Not assessed · 5 · no assessment recorded
PS4 This variant has been reported in disease databases, but no qualifying case-control analysis with p-value less than or equal to 0.05 and odds ratio greater than or equal to 4 was identified here. Available observation data therefore do not establish PS4. Details ▾Hide ▴
Rule
ENIGMA PS4 requires qualifying case-control enrichment evidence.
Evidence considered
- ClinVar pathogenic expert-panel classification is present
- No case-control OR and p-value evidence identified
Still missing
- No variant-specific case-control statistics meeting ENIGMA PS4 thresholds were identified.
Sources
PM3 No evidence was identified that this variant was observed with a second BRCA1 variant in a patient with BRCA1-related Fanconi anemia. PM3 was therefore not assessed. Details ▾Hide ▴
Rule
ENIGMA PM3 is reserved for BRCA1/2-related Fanconi anemia with biallelic observations.
Evidence considered
- No PM3-qualifying recessive-disease data identified
Still missing
- No qualifying biallelic Fanconi anemia observations were identified.
Sources
PP1 No quantitative co-segregation analysis for this variant was identified, so PP1 was not assessed. Details ▾Hide ▴
Rule
ENIGMA PP1 requires quantitative segregation evidence.
Evidence considered
- No qualifying segregation dataset identified
Still missing
- No variant-specific segregation likelihood ratio meeting ENIGMA thresholds was identified.
Sources
BS2 No qualifying observations of this variant in individuals without features of BRCA1-related Fanconi anemia were identified for the ENIGMA BS2 point system, so BS2 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BS2 requires point-based unaffected observations in the recessive-disease context.
Evidence considered
- No BS2-qualifying clinical observations identified
Still missing
- No BS2 point-based unaffected observations were identified.
Sources
BS4 No quantitative lack-of-segregation analysis for this variant was identified, so BS4 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BS4 requires quantitative lack-of-segregation evidence.
Evidence considered
- No qualifying lack-of-segregation data identified
Still missing
- No variant-specific segregation likelihood ratio supporting BS4 was identified.
Sources
Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 is defined for missense variants with the same amino acid change as a previously classified pathogenic variant, or for variants with the same demonstrated splicing effect as a known pathogenic variant. This frameshift deletion does not meet those use conditions. Details ▾Hide ▴
Rule
ENIGMA PS1 applies to qualifying missense or splice-equivalent variants, not frameshift deletions.
Evidence considered
- Variant type is frameshift
Sources
PS2 N/AThe ENIGMA BRCA1 specification marks PS2 as not applicable for this framework, so de novo evidence was not used for this case. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: PS2 not applicable.
Evidence considered
- CSPEC lists PS2 as not applicable
Sources
PM1 N/AThe ENIGMA BRCA1 specification marks PM1 as not applicable, so location in a mutational hotspot or critical domain was not used as an independent criterion for this variant. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: PM1 not applicable.
Evidence considered
- CSPEC lists PM1 as not applicable
Sources
PM4 N/AThe ENIGMA BRCA1 specification marks PM4 as not applicable, and this frameshift effect is already captured by the null-variant framework under PVS1. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: PM4 not applicable.
Evidence considered
- CSPEC lists PM4 as not applicable
Sources
PM6 N/AThe ENIGMA BRCA1 specification marks PM6 as not applicable, so assumed de novo evidence was not used for this case. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: PM6 not applicable.
Evidence considered
- CSPEC lists PM6 as not applicable
Sources
PP2 N/AThe ENIGMA BRCA1 specification marks PP2 as not applicable, so this criterion was not used. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: PP2 not applicable.
Evidence considered
- CSPEC lists PP2 as not applicable
Sources
PP3 N/APP3 in the ENIGMA BRCA1 specification is used for qualifying missense, in-frame, or non-canonical splice-impact variants. This early frameshift deletion is evaluated under the truncating-variant framework instead, so PP3 was not applied. Details ▾Hide ▴
Rule
ENIGMA PP3 applies to defined missense/in-frame/splicing contexts, not to this frameshift PVS1 scenario.
Evidence considered
- Variant type is frameshift
- SpliceAI max delta score is 0.00
Sources
BP1 N/ABP1 in the ENIGMA BRCA1 specification applies to silent, missense, or in-frame variants outside clinically important domains without predicted splice impact. This frameshift deletion does not fit that variant class. Details ▾Hide ▴
Rule
ENIGMA BP1 applies to selected non-truncating variant classes.
Evidence considered
- Variant type is frameshift
Sources
BP2 N/AThe ENIGMA BRCA1 specification marks BP2 as not applicable, so this criterion was not used. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: BP2 not applicable.
Evidence considered
- CSPEC lists BP2 as not applicable
Sources
BP3 N/AThe ENIGMA BRCA1 specification marks BP3 as not applicable, so repetitive-region in-frame evidence was not used. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: BP3 not applicable.
Evidence considered
- CSPEC lists BP3 as not applicable
Sources
BP4 N/ABP4 in the ENIGMA BRCA1 specification applies to qualifying missense, in-frame, silent, or intronic variants with no predicted impact. This early frameshift deletion is not within those use conditions. Details ▾Hide ▴
Rule
ENIGMA BP4 applies to selected non-truncating variant classes.
Evidence considered
- Variant type is frameshift
- SpliceAI max delta score = 0.00
Sources
BP6 N/AThe ENIGMA BRCA1 specification marks BP6 as not applicable, so prior benign assertions alone were not used as independent evidence. Details ▾Hide ▴
Rule
ENIGMA BRCA1/2 specification: BP6 not applicable.
Evidence considered
- CSPEC lists BP6 as not applicable
Sources
BP7 N/ABP7 in the ENIGMA BRCA1 specification is used for selected silent, intronic, or RNA-assay contexts. This coding frameshift deletion does not fit those use conditions. Details ▾Hide ▴
Rule
ENIGMA BP7 applies to qualifying silent, intronic, or RNA-only contexts.
Evidence considered
- Variant type is frameshift
Sources
Identifiers
- Gene
- BRCA1
- Transcript
- NM_007294.4
- Coding (HGVS c.)
- NM_007294.4:c.68_69del
- Protein (HGVS p.)
- NP_009225.1:p.(Glu23ValfsTer17)
- GRCh38
- chr17:43124027 ACT>A
- GRCh37
- chr17:41276044 ACT>A
Gene diagram
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
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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 BRCA1
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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
191 / 1,612,084 alleles
AF 0.000118 · 0 homozygotes · FAF 2.48e-05
gnomAD v2.1
58 / 282,442 alleles
AF 0.000205 · 0 homozygotes · FAF 5.39e-05
By genetic ancestry
gnomAD v4.1
AF 0.00012 · 191 / 1,612,084 alleles · 0 hom · FAF 2.5e-05
| Ashkenazi Jewish123 / 29,578 | 0.0042 |
| Remaining individuals20 / 62,394 | 0.00032 |
| Middle Eastern1 / 6,078 | 0.00016 |
| South Asian5 / 91,044 | 5.5e-05 |
| Admixed American3 / 59,996 | 5e-05 |
| European (non-Finnish)39 / 1,178,366 | 3.3e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, East Asian, African/African American.
gnomAD v2.1
AF 0.00021 · 58 / 282,442 alleles · 0 hom · FAF 5.4e-05
| Ashkenazi Jewish42 / 10,368 | 0.0041 |
| South Asian4 / 30,608 | 0.00013 |
| European (non-Finnish)11 / 128,780 | 8.5e-05 |
| Admixed American1 / 35,440 | 2.8e-05 |
0 alternate alleles recorded in 4 other groups: African/African American, East Asian, European (Finnish), Remaining individuals.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.00011848; MAF= 0.01185%, 191/1612084 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0041585; MAF= 0.41585%, 123/29578 alleles, homozygotes = 0); grpmax FAF= 2.478e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000205352; MAF= 0.02054%, 58/282442 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00405093; MAF= 0.40509%, 42/10368 alleles, homozygotes = 0); grpmax FAF= 5.395e-05.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/APP3 in the ENIGMA BRCA1 specification is used for qualifying missense, in-frame, or non-canonical splice-impact variants. This early frameshift deletion is evaluated under the truncating-variant framework instead, so PP3 was not applied. Details ▾Hide ▴
Rule
ENIGMA PP3 applies to defined missense/in-frame/splicing contexts, not to this frameshift PVS1 scenario.
Evidence considered
- Variant type is frameshift
- SpliceAI max delta score is 0.00
Sources
BP4 N/ABP4 in the ENIGMA BRCA1 specification applies to qualifying missense, in-frame, silent, or intronic variants with no predicted impact. This early frameshift deletion is not within those use conditions. Details ▾Hide ▴
Rule
ENIGMA BP4 applies to selected non-truncating variant classes.
Evidence considered
- Variant type is frameshift
- SpliceAI max delta score = 0.00
Sources
BP7 N/ABP7 in the ENIGMA BRCA1 specification is used for selected silent, intronic, or RNA-assay contexts. This coding frameshift deletion does not fit those use conditions. Details ▾Hide ▴
Rule
ENIGMA BP7 applies to qualifying silent, intronic, or RNA-only contexts.
Evidence considered
- Variant type is frameshift
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
191 / 1,612,084 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
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/1530970787
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/17662/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-41276044-ACT-A?dataset=gno…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-43124027-ACT-A?dataset=…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_007294.4%3Ac.68_6…
- OncoKB ↗www.oncokb.org/gene/BRCA1/E23Vfs*17
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=144950891
- 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 v4.1
This variant is present in gnomAD v4.1 (AF= 0.00011848; MAF= 0.01185%, 191/1612084 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.0041585; MAF= 0.41585%, 123/29578 alleles, homozygotes = 0); grpmax FAF= 2.478e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000205352; MAF= 0.02054%, 58/282442 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00405093; MAF= 0.40509%, 42/10368 alleles, homozygotes = 0); grpmax FAF= 5.395e-05.
ClinVar
This variant has been reported in ClinVar as Pathogenic (77 clinical laboratories) and as Pathogenic by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB classifies this variant as Oncogenic; biological effect: Loss-of-function.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV58786277, n = 5 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.