Is BRCA2 c.425+147G>T pathogenic?

BRCA2 c.425+147G>T is classified Benign in BRCA2 (ClinVar, Expert panel, 3 submitters; last evaluated 2015-01-12). Common (popmax 6.79%, mid) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

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.425+147G>T

Q: What condition is associated with BRCA2 c.425+147G>T?

BRCA2 c.425+147G>T is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary neoplastic syndrome (ClinVar).

Q: How common is BRCA2 c.425+147G>T in the general population?

BRCA2 c.425+147G>T is common (popmax 6.79%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs4942423 · VCV209643

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.79%, mid) — 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 +147	deep intronic (+147 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.31	GERP -1.2
Overall
CADD	1.559	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.79% Middle Eastern · 157/2,312 alleles

Filtering AF 6.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.43%

Overall 5.38% 33,531/623,070 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	13.2%	8
Finnishnot grpmax-eligible	9.63%	10
Ashkenazi Jewishnot grpmax-eligible	8.15%	12
Middle Easterngrpmax	6.79%	15
European (non-Finnish)	6.52%	15
Remaining individualsnot grpmax-eligible	5.66%	18
Admixed American	3.94%	25
South Asian	2.04%	49
African / African-American	1.09%	92
East Asian	0.0142%	7,022

Amish 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.425+147G>T
MANE Select: NM_000059
dbSNP: rs4942423
Type: single nucleotide variant
Location: chr13:32325331 (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 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
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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-425-plus-147g-t (accessed [today's date]).

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