Is BRCA2 p.His2440fs (c.7317del) pathogenic?

BRCA2 p.His2440fs (c.7317del) is classified Likely pathogenic in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-16). Absent from gnomAD; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.His2440fs (c.7317del)?

BRCA2 p.His2440fs (c.7317del) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.His2440fs (c.7317del) in the general population?

BRCA2 p.His2440fs (c.7317del) 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.His2440fs

c.7317del · rs2072682479 · VCV987784

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast ovarian cancer syndrome

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 14 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -1.7, phastCons 0.001

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.His2440fs
Coding: c.7317del
MANE Select: NM_000059
dbSNP: rs2072682479
Type: Deletion
Location: chr13:32355170 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2440: a UniProt-annotated variant site (no effect on homology-directed repair activity); the 'interaction with fancd2' region; the 'disordered' 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.His2440Arg Benign ★★★ same residue
BRCA2 p.His2440Asn Uncertain significance ★★ ⚠ same residue
BRCA2 p.His2440Pro Uncertain significance ★★ same residue
BRCA2 p.His2440= Likely benign ★★ same residue
BRCA2 p.His2440Leu Uncertain significance ★ same residue
BRCA2 p.His2440Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?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-his2440fs (accessed [today's date]).

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