ClinVar Miner

Submissions for variant NM_033453.4(ITPA):c.124+2T>C

dbSNP: rs1408254396
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000991064 SCV001142172 pathogenic Inosine triphosphatase deficiency 2019-05-28 criteria provided, single submitter clinical testing
DASA RCV001824157 SCV002073783 pathogenic Developmental and epileptic encephalopathy, 35 2022-02-05 criteria provided, single submitter clinical testing The c.124+2T>C variant is located in a canonical splice-site, and it is predicted to alter gene function due to either exon skipping or nonsense-mediate decay – NMD, and the variant is present in a relevant exon to the transcript - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (Clinvar ID: 804162) - PS4_supporting. This variant is not present in population databases (rs1408254396; gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000991064 SCV002968713 likely pathogenic Inosine triphosphatase deficiency 2022-05-04 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the ITPA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ITPA are known to be pathogenic (PMID: 26224535). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ITPA-related conditions. ClinVar contains an entry for this variant (Variation ID: 804162). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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