Is BRCA2 c.7435+53C>T pathogenic?

BRCA2 c.7435+53C>T is classified Benign in BRCA2 (ClinVar, Expert panel, 13 submitters; last evaluated 2015-01-12). Common (popmax 11.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.7435+53C>T?

BRCA2 c.7435+53C>T is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (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.7435+53C>T

Q: How common is BRCA2 c.7435+53C>T in the general population?

BRCA2 c.7435+53C>T is common (popmax 11.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs11147489 · VCV126136

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 11.9%, eas) — 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 +53	deep intronic (+53 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.092	GERP -3.3
Non-coding constraint	Z 0.31	1 kb window · o/e 0.97 · regional · uncalibrated
Overall
CADD	3.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.9% East Asian · 5,277/44,256 alleles

Filtering AF 11.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.5%

Overall 4.16% 66,080/1,587,692 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	11.9%	8
South Asian	11.4%	9
Admixed American	8.11%	12
Middle Eastern	5.49%	18
Remaining individualsnot grpmax-eligible	4.54%	22
Ashkenazi Jewishnot grpmax-eligible	4.05%	25
European (non-Finnish)	3.37%	30
Amishnot grpmax-eligible	2.64%	38
African / African-American	2.02%	49
Finnishnot grpmax-eligible	1.48%	67

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.7435+53C>T
MANE Select: NM_000059
dbSNP: rs11147489
Type: single nucleotide variant
Location: chr13:32355341 (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

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

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-7435-plus-53c-t (accessed [today's date]).

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