Submissions for variant NM_020964.3(EPG5):c.2718+3A>G

gnomAD frequency: 0.00032  dbSNP: rs374002995

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520041	SCV000620513	uncertain significance	not provided	2017-09-01	criteria provided, single submitter	clinical testing	The c.2718+3A>G variant in the EPG5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is not predicted to significantly affect splicing, however in the absence of RNA/functional studies, the actual effect of c.2718+3A>G in this individual is unknown. This substitution occurs at a position that is conserved across species. The c.2718+3A>G variant is observed in 5/6616 (0.075%) alleles from individuals of Finnish background, in the ExAC dataset (Lek et al., 2016). We interpret c.2718+3A>G as a variant of uncertain significance.
Invitae	RCV000687181	SCV000814734	uncertain significance	Vici syndrome	2022-10-31	criteria provided, single submitter	clinical testing	This sequence change falls in intron 14 of the EPG5 gene. It does not directly change the encoded amino acid sequence of the EPG5 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs374002995, gnomAD 0.04%). 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: 451768). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.