Is BRCA2 p.Glu2139Ile (c.6415_6416delinsAT) pathogenic?

BRCA2 p.Glu2139Ile (c.64156416delinsAT) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-11-20). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Glu2139Ile (c.6415_6416delinsAT)?

BRCA2 p.Glu2139Ile (c.6415_6416delinsAT) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Glu2139Ile (c.6415_6416delinsAT) in the general population?

BRCA2 p.Glu2139Ile (c.6415_6416delinsAT) is absent from gnomAD (gnomAD).

BRCA2 p.Glu2139Ile

c.6415_6416delinsAT · rs1064795067 · VCV421336

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic

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.Glu2139Ile
Coding: c.6415_6416delinsAT
MANE Select: NM_000059
dbSNP: rs1064795067
Type: Indel
Location: chr13:32340770 (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 p.Glu2139fs Pathogenic/Likely pathogenic ★★ same residue
BRCA2 p.Glu2139Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Glu2139Ter Pathogenic/Likely pathogenic ★★ same residue
BRCA2 p.Glu2139Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Glu2139Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Glu2139= Likely benign ★ same residue
BRCA2 c.1587delinsCA Pathogenic ★★★ same condition
BRCA2 c.8954-1_8955delinsAA 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-glu2139ile (accessed [today's date]).

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