Is BRCA2 p.Gln2899= (c.8697A>G) pathogenic?

BRCA2 p.Gln2899= (c.8697A>G) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 8 submitters; last evaluated 2017-06-29). Very rare (popmax 0.00314%, nfe); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Gln2899= (c.8697A>G)?

BRCA2 p.Gln2899= (c.8697A>G) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Gln2899= (c.8697A>G) in the general population?

BRCA2 p.Gln2899= (c.8697A>G) is very rare (popmax 0.00314%, nfe) (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 p.Gln2899=

c.8697A>G · rs786203707 · VCV187403

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.38	GERP -4.2, phastCons 0.9
Overall
CADD	11.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,180,042 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.0026% 38/1,461,876 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00314%	31,893
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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
Protein: p.Gln2899=
Coding: c.8697A>G
MANE Select: NM_000059
dbSNP: rs786203707
Type: single nucleotide variant
Location: chr13:32376734 (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 breast cancer hereditary neoplastic syndrome

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Gln2899Ter Pathogenic ★★★ same residue
BRCA2 p.Gln2899Pro Uncertain significance ★★ same residue
BRCA2 p.Gln2899Arg Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Gln2899His Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Gln2899fs Pathogenic ★★ same residue
BRCA2 p.Gln2899_Asp2900insTer Pathogenic ★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>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-p-gln2899 (accessed [today's date]).

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