Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000059.4(BRCA2):c.9372C>A (p.Asn3124Lys)

CA387761213

462524 (ClinVar)

Gene: BRCA2 (HGNC:675)

Condition: BRCA2-related cancer predisposition (MONDO:0700269)

Inheritance Mode: Autosomal dominant inheritance

UUID: 0d707dd7-0bb1-4186-8bc4-eb9044fcc52e

Approved on: 2026-01-05

Published on: 2026-01-05

HGVS expressions

NM_000059.4(BRCA2):c.9372C>A (p.Asn3124Lys)

NM_000059.4:c.9372C>A

NC_000013.11:g.32394804C>A

CM000675.2:g.32394804C>A

NC_000013.10:g.32968941C>A

CM000675.1:g.32968941C>A

NC_000013.9:g.31866941C>A

NG_012772.3:g.84325C>A

ENST00000470094.2:c.9372C>A

ENST00000528762.2:c.*739C>A

ENST00000530893.7:c.9003C>A

ENST00000665585.2:c.*934C>A

ENST00000666593.2:c.*217C>A

ENST00000700202.2:c.9321C>A

ENST00000700202.1:c.1788C>A

ENST00000700203.1:n.1499C>A

ENST00000380152.8:c.9372C>A

ENST00000544455.6:c.9372C>A

ENST00000614259.2:c.9380C>A

ENST00000665585.1:c.2250C>A

ENST00000666593.1:c.394C>A

ENST00000680887.1:c.9372C>A

ENST00000380152.7:c.9372C>A

ENST00000470094.1:c.329C>A

ENST00000544455.5:c.9372C>A

NM_000059.3:c.9372C>A

Uncertain Significance

PS3 BP4 PM2_Supporting

Evidence Links 0

Expert Panel

ENIGMA BRCA1 and BRCA2 VCEP

Criteria Specification Information

Criteria Specification: ClinGen ENIGMA BRCA1 and BRCA2 Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRCA2 Version 1.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ENIGMA BRCA1 and BRCA2 VCEP

The c.9372C>A variant in BRCA2 is a missense variant predicted to cause substitution of Asparagine by Lysine at amino acid 3124 (p.(Asn3124Lys)). 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). Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs:38417439, 39779857) (PS3 met). This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.0006, which is below the recommended threshold of 0.18 for predicting no impact on BRCA2 via protein change. A SpliceAI score of 0 predicts no impact on splicing (score threshold <0.10) (BP4 met). In summary, this variant meets the criteria to be classified as a Variant of uncertain significance for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PS3, BP4).

PS3

Reported by two calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs:38417439, 39779857) (PS3 met).

BP4

This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.0006, which is below the recommended threshold of 0.18 for predicting no impact on BRCA2 via protein change. A SpliceAI score of 0 predicts no impact on splicing (score threshold <0.10) (BP4 met).

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).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.