ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.428-2A>G

dbSNP: rs2087581122
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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 RCV001212472 SCV001384055 likely pathogenic Transcobalamin II deficiency 2023-05-26 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 942477). This variant has not been reported in the literature in individuals affected with TCN2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 3 of the TCN2 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 TCN2 are known to be pathogenic (PMID: 7980584, 20352340).
GeneDx RCV001587229 SCV001825497 pathogenic not provided 2022-05-26 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 35488219)
Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine Ramathibodi Hospital, Mahidol University RCV001730751 SCV001981507 pathogenic Pancytopenia 2021-10-17 no assertion criteria provided research The homozygous c.428-2A>G (IVS3-2A>G) variant in TCN2 was identified in a neonate with ketoacidosis and pancytopenia. The variant was identified in heterozygous state in the asymptomatic parents. This variant was absent in large population studies (genomAD database) and our whole exome in-house database of Thai populations (200 individuals). Additionally, mRNA analysis revealed exon4 skipping.

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