ClinVar Miner

Submissions for variant NM_020964.3(EPG5):c.7474T>A (p.Phe2492Ile)

dbSNP: rs1374928586
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001054881 SCV001219239 uncertain significance Vici syndrome 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with isoleucine at codon 2492 of the EPG5 protein (p.Phe2492Ile). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with EPG5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
PreventionGenetics, part of Exact Sciences RCV003413864 SCV004118071 uncertain significance EPG5-related disorder 2023-04-05 criteria provided, single submitter clinical testing The EPG5 c.7474T>A variant is predicted to result in the amino acid substitution p.Phe2492Ile. To our knowledge, this variant has not been reported in the literature. A different substitution of this amino acid (p.Phe2492Cys) has been reported in the compound heterozygous state with a loss-of-function variant in an individual with Vici syndrome (van Diemen et al. 2017. PubMed ID: 28939701). The c.7474T>A (p.Phe2492Ile) variant is reported in 0.011% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-43435621-A-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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