ClinVar Miner

Submissions for variant NM_020661.4(AICDA):c.251G>A (p.Trp84Ter)

gnomAD frequency: 0.00003  dbSNP: rs193922703
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029303 SCV000051949 likely pathogenic Hyper-IgM syndrome type 2 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
GeneDx RCV000254713 SCV000321386 pathogenic not provided 2017-02-07 criteria provided, single submitter clinical testing The W84X nonsense variant in the AICDA gene has been reported previously in association with Hyper IgM syndrome (Minegishi et al., 2000). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W84X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Invitae RCV000029303 SCV001587718 pathogenic Hyper-IgM syndrome type 2 2020-07-15 criteria provided, single submitter clinical testing Loss-of-function variants in AICDA are known to be pathogenic (PMID: 11007475). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with autosomal recessive hyper-IgM syndrome (PMID: 11112359). ClinVar contains an entry for this variant (Variation ID: 35655). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp84*) in the AICDA gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic.

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