Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000812864 | SCV000953193 | pathogenic | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs781623802, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with EVC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 656440). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg698*) in the EVC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). |
| ARUP Laboratories, |
RCV003736910 | SCV004563325 | pathogenic | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | The EVC2 c.2092C>T; p.Arg698Ter variant (rs781623802), to our knowledge, is not reported in the medical literature but is reported as pathogenic in ClinVar (Variation ID: 656440). This variant is found on only six chromosomes (6/250338 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. EVC2 loss-of-function is an established mechanism of disease, and multiple truncating variants downstream of p.Arg698Ter have been reported in affected individuals and are considered disease-causing (Valencia 2009). Based on available information, the p.Arg698Ter variant is considered to be pathogenic. References: Valencia M et al. Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling. Hum Mutat. 2009 Dec;30(12):1667-75. |