Is BRCA2 c.681+315TA[7] pathogenic?

BRCA2 c.681+315TA[7] is classified Benign in BRCA2 (ClinVar, Expert panel, 1 submitter; last evaluated 2016-09-28). Common (popmax 23.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 c.681+315TA[7]?

BRCA2 c.681+315TA[7] is associated with breast-ovarian cancer, familial, susceptibility to, 2 (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 c.681+315TA[7]

Q: How common is BRCA2 c.681+315TA[7] in the general population?

BRCA2 c.681+315TA[7] is common (popmax 23.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs397843916 · VCV264877

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 23.3%, mid) — too common for a highly-penetrant pathogenic allele

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.
Splicing
Splice region	donor +315	deep intronic (+315 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.29	GERP 0.17, phastCons 0.003
Non-coding constraint	Z 1.29	1 kb window · o/e 0.90 · regional · uncalibrated
Overall
CADD	0.937	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.3% Middle Eastern · 68/292 alleles

Filtering AF 18.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.4%

Overall 16.8% 25,443/151,364 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	27.9%	4
Middle Easterngrpmax	23.3%	4
European (non-Finnish)	18.7%	5
Finnishnot grpmax-eligible	18.7%	5
Remaining individualsnot grpmax-eligible	17.7%	6
East Asian	15.9%	6
Admixed American	15.2%	7
Ashkenazi Jewishnot grpmax-eligible	14.7%	7
African / African-American	14.2%	7
South Asian	12.1%	8

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.681+315TA[7]
MANE Select: NM_000059
dbSNP: rs397843916
Type: Microsatellite
Location: chr13:32329806 (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

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

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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-315ta-7 (accessed [today's date]).

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