Submissions for variant NM_020964.3(EPG5):c.6155A>G (p.His2052Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003338185	SCV004047177	uncertain significance	Vici syndrome		criteria provided, single submitter	clinical testing	The missense variant in c.6155A>G (p.His2052Arg) in EPG5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.His2052Arg variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has not been reported to the ClinVar database. The amino acid His at position 2052 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.His2052Arg in EPG5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS).
Labcorp Genetics (formerly Invitae), Labcorp	RCV003338185	SCV004679099	uncertain significance	Vici syndrome	2023-10-15	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2052 of the EPG5 protein (p.His2052Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EPG5 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.