rs60121553
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_147127.5(EVC2):āc.2235A>Gā(p.Glu745=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,613,900 control chromosomes in the GnomAD database, including 2,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.078 ( 1437 hom., cov: 32)
Exomes š: 0.015 ( 1376 hom. )
Consequence
EVC2
NM_147127.5 synonymous
NM_147127.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.17
Genes affected
EVC2 (HGNC:19747): (EvC ciliary complex subunit 2) This gene encodes a protein that functions in bone formation and skeletal development. Mutations in this gene, as well as in a neighboring gene that lies in a head-to-head configuration, cause Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia that is also known as chondroectodermal dysplasia. Mutations in this gene also cause acrofacial dysostosis Weyers type, also referred to as Curry-Hall syndrome, a disease that combines limb and facial abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 4-5622803-T-C is Benign according to our data. Variant chr4-5622803-T-C is described in ClinVar as [Benign]. Clinvar id is 262611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
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Synonymous conserved (PhyloP=2.16 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC2 | NM_147127.5 | c.2235A>G | p.Glu745= | synonymous_variant | 14/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.2235A>G | p.Glu745= | synonymous_variant | 14/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.1995A>G | p.Glu665= | synonymous_variant | 14/22 | 1 | A2 | ||
EVC2 | ENST00000475313.5 | c.1995A>G | p.Glu665= | synonymous_variant, NMD_transcript_variant | 14/23 | 1 | |||
EVC2 | ENST00000509670.1 | c.*628A>G | 3_prime_UTR_variant, NMD_transcript_variant | 15/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0784 AC: 11907AN: 151900Hom.: 1436 Cov.: 32
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GnomAD3 exomes AF: 0.0248 AC: 6242AN: 251330Hom.: 595 AF XY: 0.0194 AC XY: 2642AN XY: 135868
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GnomAD4 exome AF: 0.0149 AC: 21815AN: 1461882Hom.: 1376 Cov.: 32 AF XY: 0.0137 AC XY: 9985AN XY: 727244
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GnomAD4 genome ? AF: 0.0785 AC: 11931AN: 152018Hom.: 1437 Cov.: 32 AF XY: 0.0749 AC XY: 5566AN XY: 74316
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 06, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Ellis-van Creveld syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at