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.7684T>G (p.Phe2562Val)

CA025231

182243 (ClinVar)

Gene: BRCA2 (HGNC:675)

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

Inheritance Mode: Autosomal dominant inheritance

UUID: 11729bb9-a157-4483-beee-3d1d9bb5944b

Approved on: 2026-01-05

Published on: 2026-01-05

HGVS expressions

NM_000059.4:c.7684T>G

NM_000059.4(BRCA2):c.7684T>G (p.Phe2562Val)

NC_000013.11:g.32357808T>G

CM000675.2:g.32357808T>G

NC_000013.10:g.32931945T>G

CM000675.1:g.32931945T>G

NC_000013.9:g.31829945T>G

NG_012772.3:g.47329T>G

ENST00000470094.2:c.7684T>G

ENST00000528762.2:c.7684T>G

ENST00000530893.7:c.7315T>G

ENST00000665585.2:c.7684T>G

ENST00000666593.2:c.7684T>G

ENST00000700202.2:c.7684T>G

ENST00000700202.1:c.151T>G

ENST00000380152.8:c.7684T>G

ENST00000544455.6:c.7684T>G

ENST00000614259.2:c.7684T>G

ENST00000665585.1:c.249T>G

ENST00000680887.1:c.7684T>G

ENST00000380152.7:c.7684T>G

ENST00000544455.5:c.7684T>G

ENST00000614259.1:n.7684T>G

NM_000059.3:c.7684T>G

Uncertain Significance

PM2_Supporting PP3

BS3 PS3

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.7684T>G variant in BRCA2 is a missense variant predicted to cause substitution of Phenylalanine by Valine at amino acid 2562 (p.(Phe2562Val)). 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 BRCA2 missense variant has a SpliceAI score of 0.27, predicting an impact on splicing (score threshold >0.20) (PP3 met). Missense variant predicted to alter splicing, functional data considered only from assays that measure effect via mRNA and protein. Results from two calibrated studies with cDNA based design not considered for code application (PMID:38417439, 32444794). Reported by two calibrated studies with discordant results. Functional effect similar to pathogenic control variants (PMID:39779857) and similar to benign control variants (PMID:39779848) (PS3 and BS3 not 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, PP3).

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).

PP3

This BRCA2 missense variant has a SpliceAI score of 0.27, predicting an impact on splicing (score threshold >0.20) (PP3 met).

BS3

Missense variant predicted to alter splicing, functional data considered only from assays that measure effect via mRNA and protein. Results from two calibrated studies with cDNA based design not considered for code application (PMID:38417439, 32444794). Reported by two calibrated studies with discordant results. Functional effect similar to pathogenic control variants (PMID:39779857) and similar to benign control variants (PMID:39779848) (PS3 and BS3 not met).

PS3

Curation History

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