rs1221185345
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_147127.5(EVC2):c.142_151del(p.Asp49TrpfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000225 in 1,336,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R48R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_147127.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC2 | NM_147127.5 | c.142_151del | p.Asp49TrpfsTer9 | frameshift_variant | 1/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.142_151del | p.Asp49TrpfsTer9 | frameshift_variant | 1/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.-13+457_-13+466del | intron_variant | 1 | A2 | ||||
EVC2 | ENST00000475313.5 | c.-13+457_-13+466del | intron_variant, NMD_transcript_variant | 1 | |||||
EVC2 | ENST00000509670.1 | c.-106-232_-106-223del | intron_variant, NMD_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000225 AC: 3AN: 1336196Hom.: 0 AF XY: 0.00000304 AC XY: 2AN XY: 657414
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ellis-van Creveld syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 31, 2017 | - - |
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in EVC2 are known to be pathogenic (PMID: 17024374, 19810119, 19876929). This variant has not been reported in the literature in individuals with EVC2-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Asp49Trpfs*9) in the EVC2 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at