4-5584657-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_147127.5(EVC2):c.3023C>A(p.Ser1008Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. S1008S) has been classified as Benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_147127.5 stop_gained
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 | UniProt |
---|---|---|---|---|---|---|---|
EVC2 | NM_147127.5 | c.3023C>A | p.Ser1008Ter | stop_gained | 17/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.3023C>A | p.Ser1008Ter | stop_gained | 17/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.2783C>A | p.Ser928Ter | stop_gained | 17/22 | 1 | A2 | ||
EVC2 | ENST00000475313.5 | c.2783C>A | p.Ser928Ter | stop_gained, NMD_transcript_variant | 17/23 | 1 | |||
EVC2 | ENST00000509670.1 | c.*1416C>A | 3_prime_UTR_variant, NMD_transcript_variant | 18/23 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461582Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727058
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74264
ClinVar
Submissions by phenotype
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with EVC2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser1008*) 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