Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000674426 | SCV005381646 | pathogenic | Ellis-van Creveld syndrome | 2024-08-01 | criteria provided, single submitter | clinical testing | Variant summary: EVC2 c.534dupT (p.Glu179X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251446 control chromosomes. To our knowledge, no occurrence of c.534dupT in individuals affected with EVC2-related conditions has been reported. ClinVar contains an entry for this variant (Variation ID: 558195). Based on the evidence outlined above, the variant was classified as pathogenic for autosomal recessive Ellis-van Creveld syndrome. |
| Ambry Genetics | RCV002532163 | SCV003536789 | pathogenic | Inborn genetic diseases | 2021-10-08 | criteria provided, single submitter | clinical testing | The c.534dupT (p.E179*) alteration, located in exon 5 (coding exon 5) of the EVC2 gene, consists of a duplication of T at position 534, causing a translational frameshift with a predicted alternate stop codon after amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is expected to be causative of autosomal recessive Ellis-van Creveld syndrome (AR); however, its clinical significance for autosomal dominant Weyers acrofacial dysostosis (AD) is unclear. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic. |
| Labcorp Genetics |
RCV001861843 | SCV002123097 | pathogenic | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2024-11-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu179*) 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). This variant is not present in population databases (gnomAD no frequency). 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: 558195). For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000674426 | SCV000799762 | likely pathogenic | Ellis-van Creveld syndrome | 2018-05-04 | no assertion criteria provided | clinical testing | This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. |