Is BRCA2 c.7976+45G>C pathogenic?

BRCA2 c.7976+45G>C is classified Benign/Likely benign in BRCA2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-03-04). Rare (popmax 0.632%, eas); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

How common is BRCA2 c.7976+45G>C in the general population?

BRCA2 c.7976+45G>C is rare (popmax 0.632%, eas) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

BRCA2 c.7976+45G>C

Q: What condition is associated with BRCA2 c.7976+45G>C?

BRCA2 c.7976+45G>C is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary neoplastic syndrome (ClinVar).

rs11571718 · VCV223583

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.632%, eas)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +45	near-intronic (+45 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -3.5
Non-coding constraint	Z -0.74	1 kb window · o/e 1.06 · regional · uncalibrated
Overall
CADD	3.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.632% East Asian · 283/44,792 alleles

Filtering AF 0.571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.548%

Overall 0.0279% 447/1,603,300 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.632%	158
Remaining individualsnot grpmax-eligible	0.177%	565
South Asian	0.0264%	3,783
Admixed American	0.025%	3,998
African / African-American	0.0107%	9,355
European (non-Finnish)	0.000598%	167,231

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRCA2
Coding: c.7976+45G>C
MANE Select: NM_000059
dbSNP: rs11571718
Type: single nucleotide variant
Location: chr13:32362738 (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

breast-ovarian cancer, familial, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

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-45g-c (accessed [today's date]).

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