Is BRCA2 c.516+14C>T pathogenic?

BRCA2 c.516+14C>T is classified Benign/Likely benign in BRCA2 (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-02). Rare (popmax 0.217%, amr); Associated with Breast and/or ovarian cancer.

What condition is associated with BRCA2 c.516+14C>T?

BRCA2 c.516+14C>T is associated with Breast and/or ovarian cancer, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 c.516+14C>T in the general population?

BRCA2 c.516+14C>T is rare (popmax 0.217%, amr) (gnomAD).

BRCA2 c.516+14C>T

rs182828913 · VCV132764

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

rare (popmax 0.217%, amr)

Conditions

Breast and/or ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +14	near-intronic (+14 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.039	GERP -3.4
Non-coding constraint	Z 1.05	1 kb window · o/e 0.92 · regional · uncalibrated
Overall
CADD	8.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.217% Admixed American · 130/59,976 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.0136% 219/1,609,118 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.217%	461
Remaining individualsnot grpmax-eligible	0.0305%	3,280
European (non-Finnish)	0.00587%	17,041
African / African-American	0.00134%	74,882

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.516+14C>T
MANE Select: NM_000059
dbSNP: rs182828913
Type: single nucleotide variant
Location: chr13:32326296 (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 and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

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-516-plus-14c-t (accessed [today's date]).

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