ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.707T>C (p.Val236Ala)

gnomAD frequency: 0.00004  dbSNP: rs764307512
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665674 SCV000789833 uncertain significance Ellis-van Creveld syndrome 2017-02-22 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003222090 SCV003916880 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing EVC2: PM2, BP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782498 SCV005394766 uncertain significance not specified 2024-09-24 criteria provided, single submitter clinical testing Variant summary: EVC2 c.707T>C (p.Val236Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251254 control chromosomes, predominantly at a frequency of 3.5e-05 within the Non-Finnish European subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.707T>C has been reported in the literature in one individual affected with Ellis-van Creveld syndrome (example, Pangalos_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27168972). ClinVar contains an entry for this variant (Variation ID: 550823). Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV005223105 SCV005865961 uncertain significance Ellis-van Creveld syndrome; Curry-Hall syndrome 2024-04-18 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 236 of the EVC2 protein (p.Val236Ala). This variant is present in population databases (rs764307512, gnomAD 0.004%). This missense change has been observed in individual(s) with Ellis-van Creveld syndrome (PMID: 27168972). ClinVar contains an entry for this variant (Variation ID: 550823). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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