Is BRCA2 p.Asp1709fs (c.5125_5129del) pathogenic?

BRCA2 p.Asp1709fs (c.51255129del) is classified Pathogenic in BRCA2 (ClinVar, Expert panel, 2 submitters; last evaluated 2016-10-18). Absent from gnomAD; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Asp1709fs (c.5125_5129del)?

BRCA2 p.Asp1709fs (c.5125_5129del) is associated with breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Asp1709fs (c.5125_5129del) in the general population?

BRCA2 p.Asp1709fs (c.5125_5129del) is absent from gnomAD (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.Asp1709fs

c.5125_5129del · rs886040568 · VCV266851

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.13	GERP -4.8, phastCons 0.002

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Asp1709fs
Coding: c.5125_5129del
MANE Select: NM_000059
dbSNP: rs886040568
Type: Deletion
Location: chr13:32339479 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1709: the 'interaction with rad51' region; the 'interaction with polh' region

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

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Asp1709_Tyr1710insTer Pathogenic ★★★ same residue
BRCA2 p.Asp1709Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp1709Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp1709Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.316+4del Pathogenic ★★★ same condition
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del Pathogenic ★★★ same condition
BRCA2 c.7008-?_7805+?del 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-asp1709fs (accessed [today's date]).

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