rs1553836165
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_147127.5(EVC2):c.1713dupG(p.Asn572fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,594,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_147127.5 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EVC2 | NM_147127.5 | c.1713dupG | p.Asn572fs | frameshift_variant, splice_region_variant | 12/22 | ENST00000344408.10 | NP_667338.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.1713dupG | p.Asn572fs | frameshift_variant, splice_region_variant | 12/22 | 1 | NM_147127.5 | ENSP00000342144.5 |
Frequencies
GnomAD3 genomes AF: 0.00000748 AC: 1AN: 133658Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461196Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 726864
GnomAD4 genome AF: 0.00000748 AC: 1AN: 133658Hom.: 0 Cov.: 32 AF XY: 0.0000154 AC XY: 1AN XY: 64900
ClinVar
Submissions by phenotype
Jeune thoracic dystrophy Pathogenic:2
Pathogenic, no assertion criteria provided | research | Dan Cohn Lab, University Of California Los Angeles | Jun 01, 2017 | - - |
Likely pathogenic, no assertion criteria provided | research | University of Washington Center for Mendelian Genomics, University of Washington | - | - - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 25, 2022 | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 446665). This premature translational stop signal has been observed in individual(s) with asphyxiating thoracic dystrophy (PMID: 29068549). This sequence change creates a premature translational stop signal (p.Asn572Glufs*12) 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at