Is BRCA2 c.793+5G>A pathogenic?

BRCA2 c.793+5G>A is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-12-28). Very rare (popmax 0.000516%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 c.793+5G>A?

BRCA2 c.793+5G>A is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 c.793+5G>A in the general population?

BRCA2 c.793+5G>A is very rare (popmax 0.000516%, nfe) (gnomAD).

BRCA2 c.793+5G>A

rs779282053 · VCV483055

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000516%, nfe)

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 +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.8	GERP 0.4, phastCons 1
Non-coding constraint	Z 1.19	1 kb window · o/e 0.91 · regional · uncalibrated
Overall
CADD	19.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000516% European (non-Finnish) · 6/1,163,020 alleles

Filtering AF 0.000186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000416% 6/1,442,598 alleles · very rare

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.793+5G>A
MANE Select: NM_000059
dbSNP: rs779282053
Type: single nucleotide variant
Location: chr13:32331035 (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-793-plus-5g-a (accessed [today's date]).

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