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.7855T>C (p.Trp2619Arg)

CA387747058

827289 (ClinVar)

Gene: BRCA2 (HGNC:675)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: 9a3cdabb-780e-46c8-9be4-c236c211019e

Approved on: 2026-07-15

Published on: 2026-07-15

HGVS expressions

NM_000059.4(BRCA2):c.7855T>C (p.Trp2619Arg)

NM_000059.4:c.7855T>C

NC_000013.11:g.32362572T>C

CM000675.2:g.32362572T>C

NC_000013.10:g.32936709T>C

CM000675.1:g.32936709T>C

NC_000013.9:g.31834709T>C

NG_012772.3:g.52093T>C

ENST00000470094.2:c.7855T>C

ENST00000528762.2:c.7855T>C

ENST00000530893.7:c.7486T>C

ENST00000665585.2:c.7855T>C

ENST00000666593.2:c.7855T>C

ENST00000700202.2:c.7855T>C

ENST00000700202.1:c.322T>C

ENST00000380152.8:c.7855T>C

ENST00000544455.6:c.7855T>C

ENST00000614259.2:c.7863T>C

ENST00000665585.1:c.420T>C

ENST00000680887.1:c.7855T>C

ENST00000380152.7:c.7855T>C

ENST00000544455.5:c.7855T>C

ENST00000614259.1:n.7863T>C

NM_000059.3:c.7855T>C

Likely Pathogenic

PM2_Supporting PS3 PP3

BS4 BP5 PS1 PP4 PP1 PM5

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 1.2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ENIGMA BRCA1 and BRCA2 VCEP

The variant c.7855T>C in BRCA2 is a missense variant predicted to cause substitution of Tryptophan by Arginine at amino acid 2619 (p.Trp2619Arg). This variant is absent from gnomAD v4.1 (read depth ≥25x in >90% samples, PM2_Supporting met). This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.49, above the recommended threshold of 0.30 for prediction of impact on BRCA2 function via protein change. A SpliceAI score of 0.08 predicts no impact on splicing (score threshold ≤0.1) (PP3 met). Reported by three calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs:38417439, 39779857, 39779848) (PS3 met). In summary, this variant meets the criteria to be classified as a Likely pathogenic variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (PM2_Supporting, PP3, PS3).

PM2_Supporting

This variant is absent from gnomAD v4.1 (read depth ≥25x in >90% samples, PM2_Supporting met).

PS3

Reported by three calibrated studies to exhibit protein function similar to pathogenic control variants (PMIDs:38417439, 39779857, 39779848) (PS3 met).

PP3

This BRCA2 missense variant is within a key functional domain and the computational predictor BayesDel (noAF) gives a score of 0.49, above the recommended threshold of 0.30 for prediction of impact on BRCA2 function via protein change. A SpliceAI score of 0.08 predicts no impact on splicing (score threshold ≤0.1) (PP3 met).

BS4

No LR/segregations studies for this variant.

BP5

No LR/segregations studies for this variant.

PS1

(BRCA2):c.7857G>C (p.Trp2619Cys) is classified as LP by VCEP; however, there are no p.Trp2619Arg variants.

PP4

No LR/segregations studies for this variant.

PP1

No LR/segregations studies for this variant.

PM5

(BRCA2):c.7857G>C (p.Trp2619Cys) is classified as LP by VCEP; however, this code does not capture different missense substitutions.

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.