Is BRCA2 c.*271C>A pathogenic?

BRCA2 c.271C>A is classified Uncertain significance in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-25). Very rare (popmax 0.00429%, amr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.*271C>A?

BRCA2 c.*271C>A is associated with breast-ovarian cancer, familial, susceptibility to, 2, Fanconi anemia complementation group D1 (ClinVar).

How common is BRCA2 c.*271C>A in the general population?

BRCA2 c.*271C>A is very rare (popmax 0.00429%, amr) (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.*271C>A

rs868342410 · VCV881309

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00429%, amr)

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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -0.5, phastCons 0.002
Overall
CADD	1.163	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00429% Admixed American · 1/23,290 alleles

Filtering AF 0.00209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00147%

Overall 0.0025% 10/400,058 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00429%	23,290
European (non-Finnish)	0.00403%	24,834

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.*271C>A
MANE Select: NM_000059
dbSNP: rs868342410
Type: single nucleotide variant
Location: chr13:32399041 (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: Fanconi anemia complementation group D1

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-star-271c-a (accessed [today's date]).

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