Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_007294.4(BRCA1):c.5090G>A (p.Cys1697Tyr)

CA003230

37635 (ClinVar)

Gene: BRCA1
Condition: BRCA1-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 03de8501-996c-48bf-9d43-c794a465f00a
Approved on: 2024-06-12
Published on: 2024-06-12

HGVS expressions

NM_007294.4:c.5090G>A
NM_007294.4(BRCA1):c.5090G>A (p.Cys1697Tyr)
NC_000017.11:g.43063936C>T
CM000679.2:g.43063936C>T
NC_000017.10:g.41215953C>T
CM000679.1:g.41215953C>T
NC_000017.9:g.38469479C>T
NG_005905.2:g.154048G>A
ENST00000461574.2:c.5087G>A
ENST00000470026.6:c.5090G>A
ENST00000473961.6:c.4964G>A
ENST00000476777.6:c.5084G>A
ENST00000477152.6:c.5012G>A
ENST00000478531.6:c.1778G>A
ENST00000489037.2:c.5012G>A
ENST00000493919.6:c.1640G>A
ENST00000494123.6:c.5090G>A
ENST00000497488.2:c.4202G>A
ENST00000618469.2:c.5090G>A
ENST00000634433.2:c.4967G>A
ENST00000644379.2:c.5156G>A
ENST00000644555.2:c.1640G>A
ENST00000652672.2:c.4949G>A
ENST00000484087.6:c.1652G>A
ENST00000357654.9:c.5090G>A
ENST00000471181.7:c.5153G>A
ENST00000644379.1:c.1477G>A
ENST00000352993.7:c.1664G>A
ENST00000357654.7:c.5090G>A
ENST00000461221.5:c.*4873G>A
ENST00000468300.5:c.1778G>A
ENST00000471181.6:c.5153G>A
ENST00000478531.5:c.1778G>A
ENST00000484087.5:c.1403G>A
ENST00000491747.6:c.1778G>A
ENST00000493795.5:c.4949G>A
ENST00000493919.5:c.1640G>A
ENST00000586385.5:c.20G>A
ENST00000591534.5:c.563G>A
ENST00000591849.5:c.-98-13746G>A
NM_007294.3:c.5090G>A
NM_007297.3:c.4949G>A
NM_007298.3:c.1778G>A
NM_007299.3:c.1778G>A
NM_007300.3:c.5153G>A
NR_027676.1:n.5226G>A
NM_007297.4:c.4949G>A
NM_007299.4:c.1778G>A
NM_007300.4:c.5153G>A
NR_027676.2:n.5267G>A
More

Likely Pathogenic

Met criteria codes 3
PM2_Supporting PS3 PP3

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA1 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
ENIGMA BRCA1 and BRCA2 VCEP
The c.5090G>A variant in BRCA1 is a missense variant predicted to cause substitution of Cysteine by Tyrosine at amino acid 1697 (p.Cys1697Tyr). This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met). This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.386, above the recommended threshold of 0.28 for prediction of impact on BRCA1 function via protein change. SpliceAI predictor score of 0.02 suggests that the variant has no impact on splicing (score threshold <0.10) (PP3 met). Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 30209399, PMID: 30765603) (PS3 met). In summary, this variant meets the criteria to be classified as a Likely pathogenic variant for BRCA1-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PP3, PS3).
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1 (exomes only, non-cancer subset, read depth ≥25) and gnomAD v3.1 (non-cancer subset, read depth ≥25) (PM2_Supporting met).
PS3
Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs: 30209399, PMID: 30765603) (PS3 met).
Variant labelled as LOF PubMed:30209399
Variant labelled as pathogenic PubMed:30765603
PP3
This BRCA1 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.386, above the recommended threshold of 0.28 for prediction of impact on BRCA1 function via protein change. SpliceAI predictor score of 0.02 suggests that the variant has no impact on splicing (score threshold <0.10) (PP3 met).
Curation History
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