Is BRCA2 p.Ile2315= (c.6945A>C) pathogenic?

BRCA2 p.Ile2315= (c.6945A>C) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-16). Very rare (popmax 0.00167%, amr); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Ile2315= (c.6945A>C)?

BRCA2 p.Ile2315= (c.6945A>C) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Ile2315= (c.6945A>C) in the general population?

BRCA2 p.Ile2315= (c.6945A>C) is very rare (popmax 0.00167%, 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 p.Ile2315=

c.6945A>C · VCV4723350

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.66	GERP -4, phastCons 0.98
Overall
CADD	1.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,878 alleles

Overall 6.22e-05% 1/1,606,946 alleles · very rare exomes 1/1,454,698 · genomes 0/152,248 · joint denominator

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
Protein: p.Ile2315=
Coding: c.6945A>C
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32346834 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2315: the 'interaction with hsf2bp' region; a β-strand

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ile2315Val Uncertain significance ★★ same residue
BRCA2 p.Ile2315Leu Benign ★ same residue
BRCA2 p.Ile2315fs Pathogenic ★★★ same residue
BRCA2 p.Ile2315Arg Uncertain significance ★★ same residue
BRCA2 p.Ile2315Thr Uncertain significance ★ same residue
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C 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-p-ile2315 (accessed [today's date]).

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