Is BRCA2 p.Gly2274fs (c.6819delinsGT) pathogenic?

BRCA2 p.Gly2274fs (c.6819delinsGT) is classified Likely pathogenic in BRCA2 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with breast cancer.

What condition is associated with BRCA2 p.Gly2274fs (c.6819delinsGT)?

BRCA2 p.Gly2274fs (c.6819delinsGT) is associated with breast cancer (ClinVar).

How common is BRCA2 p.Gly2274fs (c.6819delinsGT) in the general population?

BRCA2 p.Gly2274fs (c.6819delinsGT) is absent from gnomAD (gnomAD).

BRCA2 p.Gly2274fs

c.6819delinsGT · rs2137530913 · VCV1048992

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

breast cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.4	GERP 0.81, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Gly2274fs
Coding: c.6819delinsGT
MANE Select: NM_000059
dbSNP: rs2137530913
Type: Indel
Location: chr13:32341174 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2274: a UniProt-annotated variant site (in bc); the 'interaction with hsf2bp' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Gly2274Val Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Gly2274del Uncertain significance ★★ same residue
BRCA2 p.Ala3205Leu Conflicting classifications of pathogenicity ★ same condition
BRCA2 p.Gly2274Arg Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Gly2274Glu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser976Ile Conflicting classifications of pathogenicity ★ same condition
BRCA2 c.631+2T>G Pathogenic ★★★ same condition
BRCA2 c.8754+4A>G Pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brca2-p-gly2274fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown