Submission Details

Submitter:

Classification:
Definitive
GENCC:100001
Gene:
Disease:
immunodeficiency, common variable, 10
Mode Of Inheritance:
Autosomal dominant
Evaluated Date:
10/13/2021
Evidence/Notes:

NFKB2 was first reported in relation to autosomal dominant common variable immunodeficiency 10 in 2013 (Chen et al., PMID: 24140114). Over 18 variants (variant type, e.g. missense, in-frame indel, nonsense, frameshift, splice, etc) that have been reported in 20 probands in 10 publications (PMIDs: 30599236, 25205549, 24888602, 25524009, 28472507, 32813180, 30941118, 24140114, 25237204, 28778864 ) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity appears to be GOF, LOF, and DN. This gene-disease association is also supported by animal models, expression studies, in vitro functional assays, and cell culture models (PMIDs: 28778864, 19524538, 12374738, 17254973, 9432973, 26851215, 9432976). In summary, NFKB2 is definitively associated with autosomal dominant common variable immunodeficiency 10. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.

PubMed IDs:
9432973 9432976 12374738 17254973 19524538 24140114 24888602 25205549 25237204 25524009 26851215 28472507 28778864 30599236 30941118 32813180
Public Report:
Assertion Criteria:
Submitter Submitted Date:
12/05/2025

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