Is BRCA2 c.6937+151A>G pathogenic?

BRCA2 c.6937+151A>G is classified Benign in BRCA2 (ClinVar, Expert panel, 2 submitters; last evaluated 2015-01-12). Common (popmax 24.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.6937+151A>G?

BRCA2 c.6937+151A>G is associated with breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

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+151A>G

Q: How common is BRCA2 c.6937+151A>G in the general population?

BRCA2 c.6937+151A>G is common (popmax 24.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs4942439 · VCV209704

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 24.7%, afr) — too common for a highly-penetrant pathogenic allele

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
Splice region	donor +151	deep intronic (+151 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.67, phastCons 0.64
Non-coding constraint	Z -0.38	1 kb window · o/e 1.03 · regional · uncalibrated
Overall
CADD	6.725	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.7% African / African-American · 13,167/53,232 alleles

Filtering AF 24.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.2%

Overall 18.5% 107,158/579,188 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	25.3%	4
African / African-Americangrpmax	24.7%	4
Amishnot grpmax-eligible	22.1%	5
Admixed American	20.4%	5
Remaining individualsnot grpmax-eligible	18.8%	5
European (non-Finnish)	18.5%	5
Ashkenazi Jewishnot grpmax-eligible	16.5%	6
Middle Eastern	14.9%	7
South Asian	12.6%	8
East Asian	5.75%	17

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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+151A>G
MANE Select: NM_000059
dbSNP: rs4942439
Type: single nucleotide variant
Location: chr13:32344804 (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

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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-151a-g (accessed [today's date]).

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