Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667487 | SCV000791944 | likely pathogenic | Ellis-van Creveld syndrome | 2017-05-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001861758 | SCV002261667 | pathogenic | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2023-12-06 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 6 of the EVC2 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 EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). This variant is present in population databases (no rsID available, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with clinical features of autosomal recessive Ellis-van Creveld syndrome (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: 552259). 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. |