rs73198165
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_147127.5(EVC2):c.2029C>T(p.Arg677Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,942 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. R677R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_147127.5 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.2029C>T | p.Arg677Ter | stop_gained | 13/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.2029C>T | p.Arg677Ter | stop_gained | 13/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.1789C>T | p.Arg597Ter | stop_gained | 13/22 | 1 | A2 | ||
EVC2 | ENST00000475313.5 | c.1789C>T | p.Arg597Ter | stop_gained, NMD_transcript_variant | 13/23 | 1 | |||
EVC2 | ENST00000509670.1 | c.*422C>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152098Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251382Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135868
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727222
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74290
ClinVar
Submissions by phenotype
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | This sequence change creates a premature translational stop signal (p.Arg677*) 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 (rs73198165, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with Ellis-van Creveld syndrome (PMID: 19810119, 22406498). ClinVar contains an entry for this variant (Variation ID: 550579). For these reasons, this variant has been classified as Pathogenic. - |
Ellis-van Creveld syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Feb 01, 2017 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 14, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at