rs777505711
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_147127.5(EVC2):βc.893delβ(p.His298ProfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. H298H) 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.893del | p.His298ProfsTer15 | frameshift_variant | 8/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.893del | p.His298ProfsTer15 | frameshift_variant | 8/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.653del | p.His218ProfsTer15 | frameshift_variant | 8/22 | 1 | A2 | ||
EVC2 | ENST00000475313.5 | c.653del | p.His218ProfsTer15 | frameshift_variant, NMD_transcript_variant | 8/23 | 1 | |||
EVC2 | ENST00000509670.1 | c.653del | p.His218ProfsTer15 | frameshift_variant, NMD_transcript_variant | 9/23 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251346Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135840
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727236
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | This sequence change creates a premature translational stop signal (p.His298Profs*15) 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). This variant is present in population databases (rs777505711, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Ellis-van Creveld syndrome (PMID: 17024374). ClinVar contains an entry for this variant (Variation ID: 552689). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 03, 2022 | - - |
Ellis-van Creveld syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jun 30, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at