ClinVar Miner

Submissions for variant NM_000531.6(OTC):c.298+2T>G

dbSNP: rs1555972538
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523661 SCV000620515 pathogenic not provided 2017-08-29 criteria provided, single submitter clinical testing The c.298+2 T>G splice site variant in the OTC gene destroys the canonical splice donor site in intron 3. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Additionally, the c.298+2 T>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although this variant has not been previously reported to our knowledge, it is expected to be a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001049435 SCV001213484 pathogenic Ornithine carbamoyltransferase deficiency 2019-02-18 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359, 16786505). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individuals affected with ornithine transcarbamylase deficiency (PMID: 25433810, 16786505, 8530002, 28815739). ClinVar contains an entry for this variant (Variation ID: 451770). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 3 of the OTC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
Genome-Nilou Lab RCV001049435 SCV002033216 pathogenic Ornithine carbamoyltransferase deficiency 2021-11-07 criteria provided, single submitter clinical testing
Molecular Genetics laboratory, Necker Hospital RCV001049435 SCV001281838 pathogenic Ornithine carbamoyltransferase deficiency no assertion criteria provided clinical testing 1 boy with a neonatal form

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