Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SIB Swiss Institute of Bioinformatics | RCV000768392 | SCV000899159 | pathogenic | Vici syndrome | 2019-01-17 | criteria provided, single submitter | curation | This variant is interpreted as a Pathogenic for Vici syndrome, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1 => Predicted nullvariant in a gene where LOF is a known mechanism of disease. PS3-Moderate => PS3 downgraded in strength to Moderate (PMID:29130391). |
Neuberg Centre For Genomic Medicine, |
RCV000768392 | SCV004047482 | likely pathogenic | Vici syndrome | criteria provided, single submitter | clinical testing | The stop gained variant c.895C>T (p.Arg299Ter) in EPG5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Pathogenic. The c.895C>T variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.001202% is reported in gnomAD. The nucleotide change c.895C>T in EPG5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. | |
Labcorp Genetics |
RCV000768392 | SCV004267367 | pathogenic | Vici syndrome | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg299*) in the EPG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EPG5 are known to be pathogenic (PMID: 23222957, 23674064). This variant is present in population databases (rs767638289, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. ClinVar contains an entry for this variant (Variation ID: 626237). For these reasons, this variant has been classified as Pathogenic. |