Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000670126 | SCV000794943 | likely pathogenic | Ellis-van Creveld syndrome | 2017-10-19 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001038169 | SCV001201625 | pathogenic | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2023-12-02 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 12 of the EVC 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 EVC are known to be pathogenic (PMID: 23220543). This variant is present in population databases (no rsID available, gnomAD 0.002%). Disruption of this splice site has been observed in individuals with Ellis-van Creveld syndrome (PMID: 17024374, 23220543). ClinVar contains an entry for this variant (Variation ID: 554484). 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV000670126 | SCV002512700 | likely pathogenic | Ellis-van Creveld syndrome | 2021-11-03 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PVS1 strong, PS4 supporting, PM2 moderate, PM3 supporting |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000670126 | SCV004803799 | likely pathogenic | Ellis-van Creveld syndrome | 2024-01-26 | criteria provided, single submitter | clinical testing | Variant summary: EVC c.1777-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.4e-06 in 156352 control chromosomes (gnomAD). c.1777-1G>A has been reported in the literature in the compound heterozygous state in an individual affected with Ellis-van Creveld syndrome (D'Asdia_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 23220543). ClinVar contains an entry for this variant (Variation ID: 554484). Based on the evidence outlined above, the variant was classified as likely pathogenic. |