ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.707-2A>C (rs1302074641)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000809734 SCV000949905 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2018-10-29 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 5 of the EVC2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). While this particular variant has not been reported in the literature, a different variant affecting the intron 5 splice acceptor (c.707-2A>G) has been observed on the opposite chromosome (in trans) from a pathogenic EVC2 variant (p.Arg885*) in an individual affected with Ellis–van Creveld syndrome (PMID: 21815252). This finding is consistent with autosomal recessive inheritance, and suggests that variants that disrupt this consensus acceptor splice site contribute to disease. 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). For these reasons, this variant has been classified as Pathogenic.

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