Is BRCA2 c.7007+2T>C pathogenic?

BRCA2 c.7007+2T>C is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2022-11-15). Very rare (popmax 0.00134%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 c.7007+2T>C?

BRCA2 c.7007+2T>C is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 c.7007+2T>C in the general population?

BRCA2 c.7007+2T>C is very rare (popmax 0.00134%, afr) (gnomAD).

BRCA2 c.7007+2T>C

rs886040937 · VCV531318

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.99	donor loss, 2 bp away · raw score · deltas
Pangolin	Δ0.83	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Non-coding constraint	Z 2.21	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,796 alleles

Overall 0.000138% 2/1,450,840 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,796
European (non-Finnish)	8.52e-05%	1,173,234

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.7007+2T>C
MANE Select: NM_000059
dbSNP: rs886040937
Type: single nucleotide variant
Location: chr13:32346898 (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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C Pathogenic ★★★ same condition
BRCA2 c.475+1G>A Pathogenic ★★★ same condition
BRCA2 c.475+1G>T Pathogenic ★★★ same condition
BRCA2 c.476-2A>G Pathogenic ★★★ same condition
BRCA2 c.517-2A>G 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-7007-plus-2t-c (accessed [today's date]).

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