Is BRCA2 c.7007+53G>A pathogenic?

BRCA2 c.7007+53G>A is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-02). Rare (popmax 0.192%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 c.7007+53G>A?

BRCA2 c.7007+53G>A is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 c.7007+53G>A in the general population?

BRCA2 c.7007+53G>A is rare (popmax 0.192%, afr) (gnomAD).

BRCA2 c.7007+53G>A

rs56014558 · VCV516245

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.192%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +53	deep intronic (+53 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -3.2
Non-coding constraint	Z 2.21	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	0.142	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.192% African / African-American · 133/69,184 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.156%

Overall 0.0123% 169/1,375,538 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.192%	520
Admixed American	0.0303%	3,303
Remaining individualsnot grpmax-eligible	0.0203%	4,917
Middle Eastern	0.0197%	5,088
South Asian	0.00128%	78,042
European (non-Finnish)	0.000708%	141,267

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+53G>A
MANE Select: NM_000059
dbSNP: rs56014558
Type: single nucleotide variant
Location: chr13:32346949 (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

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

Also linked: hereditary breast ovarian cancer syndrome

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-53g-a (accessed [today's date]).

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