ClinVar Miner

Submissions for variant NM_020964.3(EPG5):c.6232C>T (p.Arg2078Ter)

gnomAD frequency: 0.00002  dbSNP: rs587776942
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV000033118 SCV006585363 pathogenic Vici syndrome 2024-12-09 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v4.1.0 dataset (total allele frequency: 0.001%). Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000039984 /PMID: 23222957). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV004700299 SCV005201728 pathogenic not provided 2023-09-15 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28333917, 26917586, 23222957)
Labcorp Genetics (formerly Invitae), Labcorp RCV000033118 SCV004297835 pathogenic Vici syndrome 2024-08-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2078*) 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 (rs587776942, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Vici syndrome (PMID: 23222957). ClinVar contains an entry for this variant (Variation ID: 39984). For these reasons, this variant has been classified as Pathogenic.
SIB Swiss Institute of Bioinformatics RCV000033118 SCV000899147 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. PM3 => For recessive disorders, detected in trans with a pathogenic variant (PMID:23222957).
Genetic Services Laboratory, University of Chicago RCV000033118 SCV000247310 pathogenic Vici syndrome 2015-02-23 criteria provided, single submitter clinical testing
OMIM RCV000033118 SCV000056899 pathogenic Vici syndrome 2013-01-01 no assertion criteria provided literature only

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