ClinVar Miner

Submissions for variant NM_000355.4(TCN2):c.428-2_428-1del

gnomAD frequency: 0.00005  dbSNP: rs955351335
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815743 SCV000956212 pathogenic Transcobalamin II deficiency 2023-05-23 criteria provided, single submitter clinical testing This sequence change affects a 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). This variant is present in population databases (no rsID available, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with transcobalamine II deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 658845). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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