Is BRCA2 c.8487+47C>A pathogenic?

BRCA2 c.8487+47C>A is classified Benign/Likely benign in BRCA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-04). Ultra-rare (popmax 0.0696%, eas); Associated with hereditary breast carcinoma.

What condition is associated with BRCA2 c.8487+47C>A?

BRCA2 c.8487+47C>A is associated with hereditary breast carcinoma (ClinVar).

How common is BRCA2 c.8487+47C>A in the general population?

BRCA2 c.8487+47C>A is ultra-rare (popmax 0.0696%, eas) (gnomAD).

How is Hereditary breast cancer inherited?

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

BRCA2 c.8487+47C>A

rs11571744 · VCV433825

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0696%, eas)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +47	near-intronic (+47 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.63	GERP -3
Non-coding constraint	Z 1.89	1 kb window · o/e 0.86 · regional · uncalibrated
Overall
CADD	0.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0696% East Asian · 31/44,518 alleles

Filtering AF 0.0504% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0438%

Overall 0.00216% 34/1,573,904 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0696%	1,436
Remaining individualsnot grpmax-eligible	0.00491%	20,365

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.8487+47C>A
MANE Select: NM_000059
dbSNP: rs11571744
Type: single nucleotide variant
Location: chr13:32370604 (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

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

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

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>T Pathogenic ★★★ same condition
BRCA2 c.476-2A>G Pathogenic ★★★ same condition
BRCA2 c.517-2A>G Pathogenic ★★★ same condition
BRCA2 c.631+2T>G Pathogenic ★★★ same condition
BRCA2 c.632-2A>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-8487-plus-47c-a (accessed [today's date]).

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