Is BRCA2 c.7007+2428A>C pathogenic?

BRCA2 c.7007+2428A>C is classified Benign in BRCA2 (ClinVar, Expert panel, 1 submitter; last evaluated 2015-01-12). Low-frequency (popmax 4.39%, afr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.7007+2428A>C?

BRCA2 c.7007+2428A>C is associated with breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 c.7007+2428A>C in the general population?

BRCA2 c.7007+2428A>C is low-frequency (popmax 4.39%, afr) (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.7007+2428A>C

rs11571691 · VCV209731

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 4.39%, afr)

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 +2428	deep intronic (+2428 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -0.12, phastCons 0.001
Overall
CADD	0.192	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.39% African / African-American · 1,791/40,810 alleles

Filtering AF 4.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.15%

Overall 1.78% 2,670/149,988 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.39%	23
Amishnot grpmax-eligible	3.3%	30
Middle Eastern	2.4%	42
South Asian	2.37%	42
Remaining individualsnot grpmax-eligible	1.78%	56
Ashkenazi Jewishnot grpmax-eligible	1.39%	72
Admixed American	0.761%	131
European (non-Finnish)	0.748%	134
East Asian	0.427%	234
Finnishnot grpmax-eligible	0.0485%	2,062

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+2428A>C
MANE Select: NM_000059
dbSNP: rs11571691
Type: single nucleotide variant
Location: chr13:32349324 (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>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-2428a-c (accessed [today's date]).

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