Submissions for variant NM_182972.3(IRF2BP2):c.189C>A (p.His63Gln)

gnomAD frequency: 0.00003  dbSNP: rs754511640

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002002323	SCV002235319	uncertain significance	not provided	2023-08-07	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with IRF2BP2-related conditions. This variant is present in population databases (rs754511640, gnomAD 0.02%). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 63 of the IRF2BP2 protein (p.His63Gln). ClinVar contains an entry for this variant (Variation ID: 1448760). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224595	SCV003920068	uncertain significance	Immunodeficiency, common variable, 14	2022-10-13	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 0.01% [2/15210]; https://gnomad.broadinstitute.org/variant/1-234609306-G-T?dataset=gnomad_r3). This variant is also present in ClinVar (Variation ID: 1448760). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.