Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000255270 | SCV000322261 | pathogenic | not provided | 2016-02-05 | criteria provided, single submitter | clinical testing | The R340X pathogenic variant in the EVC gene has been reported previously in Ellis-van Creveldsyndrome, in an affected individual who was compound heterozygous for the R340X variant andanother protein truncating variant (Ruiz-Perez et al., 2000). This variant is predicted to cause loss ofnormal protein function either through protein truncation or nonsense-mediated mRNA decay. TheR340X variant was not observed in approximately 6500 individuals of European and AfricanAmerican ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benignvariant in these populations. We interpret R340X as a pathogenic variant. |
Rare Disease Group, |
RCV000005668 | SCV000788394 | pathogenic | Ellis-van Creveld syndrome | 2018-05-01 | criteria provided, single submitter | research | |
Invitae | RCV000807465 | SCV000947518 | pathogenic | Ellis-van Creveld syndrome; Curry-Hall syndrome | 2023-09-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg340*) in the EVC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EVC are known to be pathogenic (PMID: 23220543). This variant is present in population databases (rs121908425, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with EVC-related conditions (PMID: 10700184, 17024374, 29068549). ClinVar contains an entry for this variant (Variation ID: 5340). For these reasons, this variant has been classified as Pathogenic. |
3billion | RCV000005668 | SCV002058980 | pathogenic | Ellis-van Creveld syndrome | 2022-01-03 | criteria provided, single submitter | clinical testing | Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000005340, PMID:10700184).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000014, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Revvity Omics, |
RCV000255270 | SCV003823855 | pathogenic | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000255270 | SCV004562442 | pathogenic | not provided | 2023-09-05 | criteria provided, single submitter | clinical testing | The EVC c.1018C>T; p.Arg340Ter variant (rs121908425) is reported in the literature in multiple individuals affected with Ellis-van Creveld syndrome and Weyers acrofacial dyostosis (Ruiz-Perez 2000, Stranneheim 2021). This variant is also reported in ClinVar (Variation ID: 5340) and is found in the general population with an allele frequency of 0.001414% (4/282,890 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. Several downstream truncating variants have been described in individuals with Ellis-van Creveld syndrome and are considered pathogenic (Nguyen 2016, Ruiz-Perez 2000). Based on the available information, this variant is considered to be pathogenic. References: Nguyen TQ et al. Truncation and microdeletion of EVC/EVC2 with missense mutation of EFCAB7 in Ellis-van Creveld syndrome. Congenit Anom (Kyoto). 2016 Sep;56(5):209-16. PMID: 26748586. Ruiz-Perez VL et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet. 2000;24(3):283-286. PMID: 10700184. Stranneheim H et al. Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients. Genome Med. 2021;13(1):40. Published 2021 Mar 17. PMID: 33726816. |
OMIM | RCV000005668 | SCV000025850 | pathogenic | Ellis-van Creveld syndrome | 2000-03-01 | no assertion criteria provided | literature only | |
Dan Cohn Lab, |
RCV000516113 | SCV000612079 | pathogenic | Short-rib thoracic dysplasia 6 with or without polydactyly | 2017-06-01 | no assertion criteria provided | research | |
Counsyl | RCV000005668 | SCV000795981 | pathogenic | Ellis-van Creveld syndrome | 2017-11-26 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000005668 | SCV001454799 | pathogenic | Ellis-van Creveld syndrome | 2020-09-16 | no assertion criteria provided | clinical testing | |
University of Washington Center for Mendelian Genomics, |
RCV000516113 | SCV001479594 | likely pathogenic | Short-rib thoracic dysplasia 6 with or without polydactyly | no assertion criteria provided | research |