Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001812320 | SCV001471243 | pathogenic | not provided | 2020-02-16 | criteria provided, single submitter | clinical testing | The EVC2 c.2483G>A; p.Trp828Ter variant, to our knowledge, is not reported in the medical literature or gene-specific databases. However, a different nonsense variant in the same codon (c.2484G>A; p.Trp828Ter) has been reported in trans to another pathogenic EVC2 variant an individual affected with Ellis-van Creveld syndrome (Zhang 2012). The c.2483G>A variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, the c.2483G>A; p.Trp828Ter variant is considered to be pathogenic. References: Zhang Z et al. Identification of one novel mutation in the EVC2 gene in a Chinese family with Ellis-van Creveld syndrome. Gene. 2012 Dec 15;511(2):380-2. |
Labcorp Genetics |
RCV001871668 | SCV002231875 | pathogenic | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2021-05-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This nonsense variant has been observed in individual(s) with Ellis–van Creveld syndrome (PMID: 23026208). ClinVar contains an entry for this variant (Variation ID: 993460). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp828*) 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). |