Submissions for variant NM_153717.3(EVC):c.550G>A (p.Asp184Asn)

gnomAD frequency: 0.00194  dbSNP: rs41269549

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725205	SCV000334959	uncertain significance	not provided	2016-11-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000334802	SCV000450149	likely benign	Ellis-van Creveld syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV000725205	SCV000617141	likely benign	not provided	2019-11-29	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083825	SCV001097951	likely benign	Ellis-van Creveld syndrome; Curry-Hall syndrome	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000725205	SCV001159736	likely benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000334802	SCV001653483	uncertain significance	Ellis-van Creveld syndrome	2021-05-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479090	SCV004223693	uncertain significance	not specified	2023-11-10	criteria provided, single submitter	clinical testing	Variant summary: EVC c.550G>A (p.Asp184Asn) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0022 in 251268 control chromosomes. c.550G>A has been reported in the literature in individuals affected with congenital heart disease (Blue_2014). These report(s) do not provide unequivocal conclusions about association of the variant with Ellis-van Creveld syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 25500235). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (likely benign n=4, VUS n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000725205	SCV004810921	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	EVC: BP4, BS2
Natera, Inc.	RCV000334802	SCV001462220	likely benign	Ellis-van Creveld syndrome	2020-01-09	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000725205	SCV001740080	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000725205	SCV001800104	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000725205	SCV001974644	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000725205	SCV001977871	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003930073	SCV004743701	likely benign	EVC-related disorder	2020-02-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).