ClinVar Miner

Submissions for variant NM_020661.4(AICDA):c.568C>T (p.Arg190Ter)

dbSNP: rs769399833
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000994845 SCV001148635 pathogenic not provided 2024-03-01 criteria provided, single submitter clinical testing AICDA: PP1:Strong, PVS1:Strong, PM2, PM6, PS4:Moderate, PS3:Supporting
Invitae RCV001869384 SCV002157480 pathogenic Hyper-IgM syndrome type 2 2023-10-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg190*) in the AICDA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the AICDA protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with autosomal dominant hyper IgM syndrome (PMID: 14564357, 15893695, 32423680). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 806827). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects AICDA function (PMID: 15893695, 24591601). For these reasons, this variant has been classified as Pathogenic.
3billion RCV001869384 SCV004013706 likely pathogenic Hyper-IgM syndrome type 2 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. The variant is predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000806827 / PMID: 14564357). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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