ClinVar Miner

Submissions for variant NM_020661.4(AICDA):c.334C>T (p.Arg112Cys)

gnomAD frequency: 0.00001  dbSNP: rs1057520542
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000432589 SCV000515955 pathogenic not provided 2015-03-05 criteria provided, single submitter clinical testing The R112C variant in the AICDA gene has been reported previously in association with hyper-IgM syndrome (Minegishi et al., 2000). R112C was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In vitro function studies indicated that the R112C variant has no detectable substrate interaction (Mu et al., 2012). Therefore, this variant is considered pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000808983 SCV000949117 pathogenic Hyper-IgM syndrome type 2 2024-01-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 112 of the AICDA protein (p.Arg112Cys). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive hyper-IgM syndrome (PMID: 11112359, 15358621, 20652909). It is commonly reported in individuals of French Canadian ancestry (PMID: 11112359, 15358621, 20652909). ClinVar contains an entry for this variant (Variation ID: 379250). 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). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003912638 SCV004733007 pathogenic AICDA-related disorder 2023-12-07 no assertion criteria provided clinical testing The AICDA c.334C>T variant is predicted to result in the amino acid substitution p.Arg112Cys. This variant has been reported in the homozygous and compound heterozygous states in individuals with hyper IgM syndrome (Minegishi et al. 2000. PubMed ID: 11112359; Wang et al. 2010. PubMed ID: 20652909; Supplementary Table 2, Platt et al. 2020. PubMed ID: 32888943). This variant was also reported in the homozygous state in an individual with hyper IgM syndrome, however this patient also had a homozygous variant in ZBPB24 and a hemizygous variant in BTK (Yazdani et al. 2018. PubMed ID: 30240888). Of note, this variant has been shown to be a found variant in the French Canadian population (Minegishi et al. 2000. PubMed ID: 11112359; Mahdaviani et al. 2012. PubMed ID: 22992148). A functional study showed that this variant impacts protein function (Mu et al. 2012. PubMed ID: 22715099). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as pathogenic.

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