Is BRCA2 c.*8C>T pathogenic?

BRCA2 c.8C>T is classified Uncertain significance in BRCA2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-10). Absent from gnomAD v4.1; Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 c.*8C>T?

BRCA2 c.*8C>T is associated with BRCA2-related cancer predisposition (ClinVar).

How common is BRCA2 c.*8C>T in the general population?

BRCA2 c.*8C>T is absent from gnomAD v4.1 (gnomAD).

BRCA2 c.*8C>T

rs747134610 · VCV495426

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

BRCA2-related cancer predisposition

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP 1.3, phastCons 0.43
Non-coding constraint	Z 1.97	1 kb window · o/e 0.86 · regional · uncalibrated
Overall
CADD	7.775	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Coding: c.*8C>T
MANE Select: NM_000059
dbSNP: rs747134610
Type: single nucleotide variant
Location: chr13:32398778 (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

BRCA2-related cancer predisposition — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 c.517-2A>G Pathogenic ★★★ same condition
BRCA2 c.631+2T>G Pathogenic ★★★ same condition
BRCA2 c.631+4A>G Likely pathogenic ★★★ same condition
BRCA2 c.632-3C>G Likely pathogenic ★★★ same condition
BRCA2 c.6938-2A>G Pathogenic ★★★ same condition
BRCA2 c.7805+3A>C Likely pathogenic ★★★ same condition
BRCA2 c.7976+5G>T Pathogenic ★★★ same condition
BRCA2 c.7977-1G>C 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-star-8c-t (accessed [today's date]).

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