Is BRCA2 p.Asn1878del (c.5629AAC[1]) pathogenic?

BRCA2 p.Asn1878del (c.5629AAC[1]) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 9 submitters; last evaluated 2024-06-11). Very rare (popmax 0.00223%, eas); Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Asn1878del (c.5629AAC[1])?

BRCA2 p.Asn1878del (c.5629AAC[1]) is associated with BRCA2-related cancer predisposition, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Asn1878del (c.5629AAC[1]) in the general population?

BRCA2 p.Asn1878del (c.5629AAC[1]) is very rare (popmax 0.00223%, eas) (gnomAD).

BRCA2 p.Asn1878del

c.5629AAC[1] · rs794727015 · VCV193790

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

BRCA2-related cancer predisposition

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 0.94	GERP -1.4, phastCons 0.069

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,854 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,459,044 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,854
European (non-Finnish)	0.000424%	235,845

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.

ClinGen expert panel — ENIGMA BRCA1 and BRCA2 VCEP

Likely Benign for BRCA2-related cancer predisposition. Applied ACMG criteria (verbatim):

BP1_Strong

Curation rationale (ClinGen, verbatim)

The c.5632_5634del variant in BRCA2 is predicted to cause a change in the length of the protein due to an in-frame deletion of one amino acid (p.Asn1878del). This variant is present in gnomAD v2.1 (exomes only, non-cancer subset) or gnomAD v3.1 (non-cancer subset) but is below the ENIGMA BRCA1/2 VCEP threshold >0.00002 for BS1_Supporting (PM2_Supporting, BS1, and BA1 are not met). This in-frame deletion variant is located outside of a key functional domain and was not predicted to alter mRNA splicing using the SpliceAI predictor (score 0.01, score threshold <0.1) (BP1_Strong met). In summary, this variant meets the criteria to be classified as a Likely benign variant for BRCA2-related cancer predisposition based on the ACMG/AMP criteria applied as specified by the ENIGMA BRCA1/2 VCEP (BP1_Strong).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Variant & gene context

Gene: BRCA2
Protein: p.Asn1878del
Coding: c.5629AAC[1]
MANE Select: NM_000059
dbSNP: rs794727015
Type: Microsatellite
Location: chr13:32339984 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1878: the 'interaction with rad51' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome familial colorectal cancer type X

Similar variants

BRCA2 p.Asn1878= Likely benign ★★★ same residue
BRCA2 p.Asn1878fs Pathogenic/Likely pathogenic ★★ same residue
BRCA2 p.Asn1878Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asn1878His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asn1878Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala1439fs Pathogenic ★★★ same condition
BRCA2 p.Ala1725Ter Pathogenic ★★★ same condition
BRCA2 p.Arg155_Asp156insTer 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-asn1878del (accessed [today's date]).

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