rs144730069
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_147127.5(EVC2):c.864C>T(p.Asn288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0043 in 1,614,144 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0031 ( 8 hom., cov: 33)
Exomes 𝑓: 0.0044 ( 23 hom. )
Consequence
EVC2
NM_147127.5 synonymous
NM_147127.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.101
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=-0.85).
BP6
?
Variant 4-5681266-G-A is Benign according to our data. Variant chr4-5681266-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 284852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.101 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00314 (478/152300) while in subpopulation NFE AF= 0.00421 (286/68012). AF 95% confidence interval is 0.0038. There are 8 homozygotes in gnomad4. There are 209 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC2 | NM_147127.5 | c.864C>T | p.Asn288= | synonymous_variant | 7/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.864C>T | p.Asn288= | synonymous_variant | 7/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.624C>T | p.Asn208= | synonymous_variant | 7/22 | 1 | A2 | ||
EVC2 | ENST00000475313.5 | c.624C>T | p.Asn208= | synonymous_variant, NMD_transcript_variant | 7/23 | 1 | |||
EVC2 | ENST00000509670.1 | c.624C>T | p.Asn208= | synonymous_variant, NMD_transcript_variant | 8/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00314 AC: 478AN: 152182Hom.: 8 Cov.: 33
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GnomAD3 exomes AF: 0.00226 AC: 568AN: 251464Hom.: 1 AF XY: 0.00227 AC XY: 309AN XY: 135910
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GnomAD4 exome AF: 0.00442 AC: 6459AN: 1461844Hom.: 23 Cov.: 32 AF XY: 0.00427 AC XY: 3103AN XY: 727222
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GnomAD4 genome ? AF: 0.00314 AC: 478AN: 152300Hom.: 8 Cov.: 33 AF XY: 0.00281 AC XY: 209AN XY: 74480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 28, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | EVC2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 13, 2020 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 07, 2015 | - - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Ellis-van Creveld syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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