Is BRCA2 c.7976+5G>T pathogenic?

BRCA2 c.7976+5G>T is classified Pathogenic in BRCA2 (ClinVar, Expert panel, 9 submitters; last evaluated 2026-09-21). Absent from gnomAD v4.1; Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 c.7976+5G>T?

BRCA2 c.7976+5G>T is associated with BRCA2-related cancer predisposition, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 c.7976+5G>T in the general population?

BRCA2 c.7976+5G>T is absent from gnomAD v4.1 (gnomAD).

BRCA2 c.7976+5G>T

rs786201180 · VCV462463

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 9 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

BRCA2-related cancer predisposition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	Δ0.89	donor loss, 5 bp away · raw score · deltas
Pangolin	Δ0.77	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.4	GERP 2.5, phastCons 1
Non-coding constraint	Z -0.74	1 kb window · o/e 1.06 · regional · uncalibrated
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Coding: c.7976+5G>T
MANE Select: NM_000059
dbSNP: rs786201180
Type: single nucleotide variant
Location: chr13:32362698 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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

Disease context

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 2 hereditary neoplastic syndrome

Similar variants

BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C Pathogenic ★★★ same condition
BRCA2 c.475+1G>A Pathogenic ★★★ same condition
BRCA2 c.475+1G>T Pathogenic ★★★ same condition
BRCA2 c.476-2A>G Pathogenic ★★★ same condition
BRCA2 c.517-2A>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-c-7976-plus-5g-t (accessed [today's date]).

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