ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.942G>A (p.Trp314Ter)

dbSNP: rs763363403
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665893 SCV000790089 likely pathogenic Ellis-van Creveld syndrome 2017-03-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001207757 SCV001379123 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2023-10-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp314*) 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 present in population databases (rs763363403, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with Ellis-van Creveld syndrome (PMID: 26580685). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Trp234*. ClinVar contains an entry for this variant (Variation ID: 550977). For these reasons, this variant has been classified as Pathogenic.
Neuberg Centre For Genomic Medicine, NCGM RCV000665893 SCV004048583 pathogenic Ellis-van Creveld syndrome criteria provided, single submitter clinical testing The stop gained variant has been reported previously in homozygous state in a family affected with Ellis-van Creveld syndrome (Aziz A. et al., 2016). The p.Trp314Ter variant is reported with the allele frequency (0.0008%) in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar with varying interpretations: Pathogenic/ Likely Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. No significant reportable EVC2 variant was detected in the spouse.
PreventionGenetics, part of Exact Sciences RCV003420174 SCV004108655 pathogenic EVC2-related disorder 2022-12-15 criteria provided, single submitter clinical testing The EVC2 c.942G>A variant is predicted to result in premature protein termination (p.Trp314*). This variant has been reported in the homozygous state in at least two individuals with Ellis-van Creveld syndrome (Aziz et al 2016. PubMed ID: 26580685; Eftekhariyazdi et al 2020. PubMed ID: 32072716). This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-5667305-C-T). Nonsense variants in EVC2 are expected to be pathogenic. This variant is interpreted as pathogenic.

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