Submissions for variant NM_147127.5(EVC2):c.913G>T (p.Ala305Ser)

gnomAD frequency: 0.00083  dbSNP: rs150367317

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000550439	SCV000634711	benign	Ellis-van Creveld syndrome; Curry-Hall syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000734269	SCV000862394	likely benign	not specified	2018-08-02	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000734269	SCV001157548	uncertain significance	not specified	2019-06-06	criteria provided, single submitter	clinical testing	The EVC2 c.[904T>A; c.913G>T]; p.[Phe302Ile; p.Ala305Ser] complex variant (rs138728350, rs150367317), to our knowledge, is not reported in the medical literature or gene specific databases. The individual variants are reported separately as benign or likely benign in ClinVar (Variation ID: 461811, 461812), but are found in cis in the Genome Aggregation Database with an overall allele frequency of 0.05% (145/282808 alleles, including 2 homozygotes) in the general population. The phenylalanine at codon 302 and the alanine at codon 305 are both highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that each variant is deleterious. Due to limited information, the clinical significance of the complex variant is uncertain at this time.
Illumina Laboratory Services, Illumina	RCV001151786	SCV001312956	likely benign	Ellis-van Creveld syndrome	2017-09-12	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV001567553	SCV001791262	likely benign	not provided	2021-01-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004751586	SCV005351620	uncertain significance	EVC2-related disorder	2024-04-04	no assertion criteria provided	clinical testing	The EVC2 c.913G>T variant is predicted to result in the amino acid substitution p.Ala305Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.078% of alleles in individuals of South Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.