chr4-5615512-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_147127.5(EVC2):c.2739G>C(p.Lys913Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 1,614,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_147127.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251470Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135910
GnomAD4 exome AF: 0.0000588 AC: 86AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727246
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74480
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Pathogenic:1Uncertain:1
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Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Uncertain:2
This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 913 of the EVC2 protein (p.Lys913Asn). This variant is present in population databases (rs180747811, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with EVC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 446693). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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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not specified Uncertain:1
Variant summary: EVC2 c.2739G>C (p.Lys913Asn) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251470 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in EVC2 causing Ellis-van Creveld syndrome (0.00012 vs 0.0029), allowing no conclusion about variant significance. c.2739G>C has been reported in the literature in at least one individual affected with Ellis-van Creveld syndrome. This report does not provide unequivocal conclusions about association of the variant with Ellis-van Creveld syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
not provided Uncertain:1
In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29068549) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at