Is BRCA2 c.681+1del pathogenic?

BRCA2 c.681+1del is classified Likely pathogenic in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). Absent from gnomAD; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 c.681+1del?

BRCA2 c.681+1del is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 c.681+1del in the general population?

BRCA2 c.681+1del 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 c.681+1del

rs2548517073 · VCV2730345

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

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	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.7	GERP -2.9, phastCons 0.52
Non-coding constraint	Z 1.29	1 kb window · o/e 0.90 · regional · uncalibrated

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
Coding: c.681+1del
MANE Select: NM_000059
dbSNP: rs2548517073
Type: Deletion
Location: chr13:32329493 (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

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 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del Pathogenic ★★★ same condition
BRCA2 c.8312del Pathogenic ★★★ same condition
BRCA2 c.8633-24_8634del Pathogenic ★★★ same condition
BRCA2 c.8756del Pathogenic ★★★ same condition
BRCA2 c.9403del Pathogenic ★★★ same condition
BRCA2 p.Ala1109fs Pathogenic ★★★ same condition
BRCA2 p.Ala1393fs 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-c-681-plus-1del (accessed [today's date]).

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