ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.1708C>T (p.Gln570Ter)

gnomAD frequency: 0.00005  dbSNP: rs769864196
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666197 SCV000790449 pathogenic Ellis-van Creveld syndrome 2017-03-21 criteria provided, single submitter clinical testing
Invitae RCV001245243 SCV001418516 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2023-12-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln570*) 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 (rs769864196, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with Ellis–van Creveld syndrome or short-rib polydactyly syndromes (PMID: 17024374, 19876929, 29068549). ClinVar contains an entry for this variant (Variation ID: 446664). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001574376 SCV001801187 pathogenic not provided 2023-01-30 criteria provided, single submitter clinical testing Nonsense 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: 25525159, 17024374, 34313030, 19876929, 29068549)
Revvity Omics, Revvity RCV001574376 SCV002022227 pathogenic not provided 2023-12-05 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001245243 SCV002811666 pathogenic Ellis-van Creveld syndrome; Curry-Hall syndrome 2022-01-19 criteria provided, single submitter clinical testing
Lifecell International Pvt. Ltd RCV000666197 SCV003924054 pathogenic Ellis-van Creveld syndrome criteria provided, single submitter clinical testing A Homozygote, Nonsense variant c.1708C>T in Exon 11 of the EVC2 gene that results in the amino acid substitution p.Gln570* was identified. The observed variant has a maximum allele frequency of 0.00003/0.00003% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (Clinvar ID: 446664). This disorder has previously been reported in the patient affected skeletal ciliopathies (Zhang W et. al 2017) Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.
Dan Cohn Lab, University Of California Los Angeles RCV000666197 SCV000612087 pathogenic Ellis-van Creveld syndrome 2017-06-01 no assertion criteria provided research
Dan Cohn Lab, University Of California Los Angeles RCV000515819 SCV000612091 pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly 2017-06-01 no assertion criteria provided research
Dan Cohn Lab, University Of California Los Angeles RCV000516102 SCV000612119 pathogenic Type IV short rib polydactyly syndrome 2017-06-01 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000516102 SCV001479699 likely pathogenic Type IV short rib polydactyly syndrome no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000515819 SCV001479750 likely pathogenic Short-rib thoracic dysplasia 6 with or without polydactyly no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000666197 SCV001479928 likely pathogenic Ellis-van Creveld syndrome no assertion criteria provided research

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