Is BRCA2 c.6937+565T>C pathogenic?

BRCA2 c.6937+565T>C is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-03-03). Rare (popmax 0.68%, mid); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.6937+565T>C?

BRCA2 c.6937+565T>C is associated with breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 c.6937+565T>C in the general population?

BRCA2 c.6937+565T>C is rare (popmax 0.68%, mid) (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.6937+565T>C

rs11571675 · VCV434534

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.68%, mid)

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 +565	deep intronic (+565 nt into the intron)
SpliceAI	Δ0.34	donor gain, 24 bp away · raw score · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.2	GERP -0.59, phastCons 1
Non-coding constraint	Z 1.88	1 kb window · o/e 0.86 · regional · uncalibrated
Overall
CADD	14.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.68% Middle Eastern · 2/294 alleles

Filtering AF 0.282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.268%

Overall 0.192% 292/152,268 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.68%	147
Amishnot grpmax-eligible	0.329%	304
European (non-Finnish)	0.316%	316
Remaining individualsnot grpmax-eligible	0.19%	528
Admixed American	0.163%	612
Finnishnot grpmax-eligible	0.113%	886
Ashkenazi Jewishnot grpmax-eligible	0.0865%	1,156
African / African-American	0.0649%	1,540
South Asian	0.0207%	4,830

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.6937+565T>C
MANE Select: NM_000059
dbSNP: rs11571675
Type: single nucleotide variant
Location: chr13:32345218 (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

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-6937-plus-565t-c (accessed [today's date]).

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