Submissions for variant NM_153717.3(EVC):c.2276G>A (p.Ser759Asn)

gnomAD frequency: 0.00025  dbSNP: rs201776972

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000331568	SCV000450306	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000971701	SCV001119360	likely benign	Ellis-van Creveld syndrome; Curry-Hall syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003278784	SCV003987658	uncertain significance	Inborn genetic diseases	2023-05-31	criteria provided, single submitter	clinical testing	The c.2276G>A (p.S759N) alteration is located in exon 15 (coding exon 15) of the EVC gene. This alteration results from a G to A substitution at nucleotide position 2276, causing the serine (S) at amino acid position 759 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics	RCV004710996	SCV005256699	likely benign	not provided		criteria provided, single submitter	not provided
GeneDx	RCV004710996	SCV005401628	uncertain significance	not provided	2024-05-01	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003950234	SCV004761813	likely benign	EVC-related disorder	2020-02-20	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).