Submissions for variant NM_147127.5(EVC2):c.3405_3411del (p.Gly1136fs)

dbSNP: rs750396637

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000176128	SCV000227731	pathogenic	not provided	2018-07-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001205094	SCV001376330	pathogenic	Ellis-van Creveld syndrome; Curry-Hall syndrome	2023-11-30	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly1136Argfs*6) 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 (rs750396637, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive Ellis-van Creveld syndrome (PMID: 19810119, 29068549). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 195541). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000176128	SCV001874262	pathogenic	not provided	2024-07-31	criteria provided, single submitter	clinical testing	Identified in a patient with Ellis-van Creveld syndrome in published literature (PMID: 19810119); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29068549, 19810119)
Dan Cohn Lab, University Of California Los Angeles	RCV000515904	SCV000612083	pathogenic	Jeune thoracic dystrophy	2017-06-01	no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV000515904	SCV001479598	likely pathogenic	Jeune thoracic dystrophy		no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV004751334	SCV005354886	pathogenic	EVC2-related disorder	2024-07-15	no assertion criteria provided	clinical testing	The EVC2 c.3405_3411del7 variant is predicted to result in a frameshift and premature protein termination (p.Gly1136Argfs*6). This variant was reported in the compound heterozygous state in an individual with Ellis-van Creveld syndrome (Valencia et al. 2009. PubMed ID: 19810119) and in the compound heterozygous state in an individual with asphixiating thoracic dystrophy (Supplemental Table S2, Zhang et al. 2017. PubMed ID: 29068549). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. Frameshift variants in EVC2 are expected to be pathogenic. This variant is interpreted as pathogenic.