Is BRCA2 c.316+5G>A pathogenic?

BRCA2 c.316+5G>A is classified Pathogenic in BRCA2 (ClinVar, Expert panel, 19 submitters; last evaluated 2018-04-01). Very rare (popmax 8.5e-05%, nfe); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.316+5G>A?

BRCA2 c.316+5G>A is associated with breast-ovarian cancer, familial, susceptibility to, 2, urinary bladder cancer, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 c.316+5G>A in the general population?

BRCA2 c.316+5G>A is very rare (popmax 8.5e-05%, nfe) (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.316+5G>A

rs81002840 · VCV51409

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 19 submitters

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

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	Δ0.73	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3	GERP 0.003, phastCons 1
Non-coding constraint	Z 1.39	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	17.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,098 alleles

Overall 6.86e-05% 1/1,457,316 alleles · very rare

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.316+5G>A
MANE Select: NM_000059
dbSNP: rs81002840
Type: single nucleotide variant
Location: chr13:32319330 (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: urinary bladder cancer hereditary breast ovarian cancer syndrome medulloblastoma Wilms tumor 1 Fanconi anemia complementation group D1 glioma susceptibility 3 pancreatic cancer, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma prostate cancer, hereditary

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>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
BRCA2 c.631+2T>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-316-plus-5g-a (accessed [today's date]).

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