Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000549564 | SCV000626060 | pathogenic | Ellis-van Creveld syndrome | 2017-05-03 | criteria provided, single submitter | clinical testing | This sequence change deletes 1 nucleotide and inserts 2 nucleotides in exon 21 of the EVC2 mRNA (c.3634delinsGA), causing a frameshift at codon 1212. This creates a premature translational stop signal in the last exon of the EVC2 mRNA (p.Leu1212Aspfs*53). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 97 amino acids of the EVC2 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a EVC2-related disease. A different truncation downstream of this variant (p.Ser1220Argfs*3) has been determined to be pathogenic (PMID: 12571802, 19810119). This suggests that deletion of this region of the EVC2 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |