ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.3080_3107del (p.Lys1027fs)

dbSNP: rs1391194715
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001236098 SCV001408810 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2023-07-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 962271). This variant has not been reported in the literature in individuals affected with EVC2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Lys1027Argfs*23) 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).
Ambry Genetics RCV002563846 SCV003718855 pathogenic Inborn genetic diseases 2021-10-08 criteria provided, single submitter clinical testing The c.3080_3107del28 (p.K1027Rfs*23) alteration, located in exon 18 (coding exon 18) of the EVC2 gene, consists of a deletion of 28 nucleotides from position 3080 to 3107, causing a translational frameshift with a predicted alternate stop codon after 23 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the supporting evidence, this variant is expected to be causative of autosomal recessive Ellis-van Creveld syndrome (AR); however, its clinical significance for autosomal dominant Weyers acrofacial dysostosis (AD) is unclear. Based on data from gnomAD, the EVC2 c.3080_3107del28 (p.L1027Rfs*23) alteration has an overall frequency of <0.01% (2/247046) total alleles studied. The highest observed frequency was 0.01% (2/34246) of Latino/Admixed American alleles. Based on the available evidence, this alteration is classified as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.