Is BRCA2 p.Lys2170fs (c.6509_6513delinsGTC) pathogenic?

BRCA2 p.Lys2170fs (c.65096513delinsGTC) is classified Pathogenic in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Lys2170fs (c.6509_6513delinsGTC)?

BRCA2 p.Lys2170fs (c.6509_6513delinsGTC) is associated with BRCA2-related cancer predisposition (ClinVar).

BRCA2 p.Lys2170fs

c.6509_6513delinsGTC · VCV3386253

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

BRCA2-related cancer predisposition

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 11 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.4	GERP -3.9

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

Variant & gene context

Gene: BRCA2
Protein: p.Lys2170fs
Coding: c.6509_6513delinsGTC
MANE Select: NM_000059
Type: Indel
Location: chr13:32340864 (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

BRCA2-related cancer predisposition — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 c.8954-1_8955delinsAA Pathogenic ★★★ same condition
BRCA2 p.Arg2799fs Pathogenic ★★★ same condition
BRCA2 p.Glu2856fs Pathogenic ★★★ same condition
BRCA2 p.Phe1870Ter Pathogenic ★★★ same condition
BRCA2 c.476-4_476-1delinsT Pathogenic/Likely pathogenic ★★ same condition
BRCA2 p.Lys2013fs Likely pathogenic ★ same condition
BRCA2 p.Lys2170Arg Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Lys2170Glu Conflicting classifications of pathogenicity ★ same residue

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-lys2170fs (accessed [today's date]).

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