Is BRCA2 p.Asp2723= (c.8169T>C) pathogenic?

BRCA2 p.Asp2723= (c.8169T>C) is classified Likely benign in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-23). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Asp2723= (c.8169T>C)?

BRCA2 p.Asp2723= (c.8169T>C) is associated with hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Asp2723= (c.8169T>C) in the general population?

BRCA2 p.Asp2723= (c.8169T>C) is very rare (popmax 8.47e-05%, 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.Asp2723=

c.8169T>C · rs1060502432 · VCV462469

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -4.2, phastCons 0.001
Overall
CADD	3.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,870 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
Protein: p.Asp2723=
Coding: c.8169T>C
MANE Select: NM_000059
dbSNP: rs1060502432
Type: single nucleotide variant
Location: chr13:32363371 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2723: a UniProt-annotated variant site (in bc; pathogenic; major splicing aberration identified with this mutant; reduced homology-directed repair activity); a UniProt-annotated variant site (in bc; pathogenic; disrupts interaction with sem1 promoting interaction with xpo1 and brca2 cytoplasmic localization; in heterozygous state promotes rad51 cytoplasmic localization; reduced homology-directed repair activity); the 'interaction with sem1' 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

Also linked: hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Asp2723Ala Pathogenic ★★★ same residue
BRCA2 p.Asp2723Gly Pathogenic ★★★ same residue
BRCA2 p.Asp2723His Pathogenic ★★★ same residue
BRCA2 p.Asp2723Val Pathogenic/Likely pathogenic ★★ same residue
BRCA2 p.Asp2723Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp2723Glu Conflicting classifications of pathogenicity ★ ⚠ 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-asp2723 (accessed [today's date]).

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