ClinVar Miner

Submissions for variant NM_020661.4(AICDA):c.260G>C (p.Cys87Ser)

gnomAD frequency: 0.00002  dbSNP: rs1260264247
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001208331 SCV001379711 pathogenic Hyper-IgM syndrome type 2 2024-10-24 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 87 of the AICDA protein (p.Cys87Ser). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive hyper-IgM syndrome (PMID: 21192628; internal data). ClinVar contains an entry for this variant (Variation ID: 939010). 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. Experimental studies have shown that this missense change affects AICDA function (PMID: 22715099). This variant disrupts the p.Cys87 amino acid residue in AICDA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14962793, 15358621, 22715099, 24349193, 25025377). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV001208331 SCV002512613 likely pathogenic Hyper-IgM syndrome type 2 2021-11-30 criteria provided, single submitter clinical testing ACMG classification criteria: PS3 supporting, PS4 supporting, PM2 moderate, PM3 supporting, PP3 supporting
PreventionGenetics, part of Exact Sciences RCV003405393 SCV004106873 pathogenic AICDA-related disorder 2023-08-14 criteria provided, single submitter clinical testing The AICDA c.260G>C variant is predicted to result in the amino acid substitution p.Cys87Ser. This variant has been reported in the homozygous state in multiple individuals with hyper-IgM syndrome (Durandy et al. 2006. PubMed ID: 16964591; Silva and Da Costa. 2010. PubMed ID: 21192628; Cabral-Marques et al. 2014. PubMed ID: 24402618). An in vitro experimental study suggests this variant impacts protein function (Mu et al. 2012. PubMed ID: 22715099). This variant is reported in 0.0085% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-8757978-C-G). This variant is interpreted as pathogenic.

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