Is BRCA2 p.Arg645del (c.1932AAG[1]) pathogenic?

BRCA2 p.Arg645del (c.1932AAG[1]) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Arg645del (c.1932AAG[1])?

BRCA2 p.Arg645del (c.1932AAG[1]) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

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.Arg645del

c.1932AAG[1] · VCV3663764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.91	GERP -2.8, phastCons 0.015

Variant & gene context

Gene: BRCA2
Protein: p.Arg645del
Coding: c.1932AAG[1]
MANE Select: NM_000059
Type: Microsatellite
Location: chr13:32336287 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 645: the 'interaction with npm1' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — 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.Arg645fs Pathogenic ★★★ same residue
BRCA2 p.Arg645Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg645Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg645= Likely benign ★ same residue
BRCA2 p.Ala1439fs Pathogenic ★★★ same condition
BRCA2 p.Ala1725Ter Pathogenic ★★★ same condition
BRCA2 p.Arg155_Asp156insTer Pathogenic ★★★ same condition
BRCA2 p.Arg2108_Val2109insTer 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-arg645del (accessed [today's date]).

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