Is BRCA2 c.7007+503A>G pathogenic?

BRCA2 c.7007+503A>G is classified Benign in BRCA2 (ClinVar, Expert panel, 2 submitters; last evaluated 2015-01-12). Common (popmax 11.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.7007+503A>G?

BRCA2 c.7007+503A>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.7007+503A>G

Q: How common is BRCA2 c.7007+503A>G in the general population?

BRCA2 c.7007+503A>G is common (popmax 11.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs11571684 · VCV209720

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 11.4%, sas) — 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 +503	deep intronic (+503 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -0.46, phastCons 0.07
Non-coding constraint	Z -0.87	1 kb window · o/e 1.07 · regional · uncalibrated
Overall
CADD	5.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.4% South Asian · 552/4,822 alleles

Filtering AF 10.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.3%

Overall 4.1% 6,239/152,282 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	11.4%	9
East Asian	10%	10
Admixed American	9.78%	10
Remaining individualsnot grpmax-eligible	4.74%	21
Ashkenazi Jewishnot grpmax-eligible	4.41%	23
European (non-Finnish)	3.44%	29
Middle Eastern	3.4%	29
Amishnot grpmax-eligible	2.63%	38
African / African-American	2.13%	47
Finnishnot grpmax-eligible	1.46%	68

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.7007+503A>G
MANE Select: NM_000059
dbSNP: rs11571684
Type: single nucleotide variant
Location: chr13:32347399 (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-7007-plus-503a-g (accessed [today's date]).

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