Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV003333948 | SCV004042537 | pathogenic | not provided | 2023-09-01 | criteria provided, single submitter | clinical testing | AICDA: PM3:Strong, PM2, PM5, PP3, PS3:Supporting |
Labcorp Genetics |
RCV000005433 | SCV004295836 | pathogenic | Hyper-IgM syndrome type 2 | 2023-08-01 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met139 amino acid residue in AICDA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 27142677). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects AICDA function (PMID: 22715099). 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. ClinVar contains an entry for this variant (Variation ID: 5126). This missense change has been observed in individuals with autosomal recessive hyper IgM syndrome (HIGM) (PMID: 11007475, 16964591). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 139 of the AICDA protein (p.Met139Val). |
OMIM | RCV000005433 | SCV000025615 | pathogenic | Hyper-IgM syndrome type 2 | 2000-09-01 | no assertion criteria provided | literature only |