Submissions for variant NM_020964.3(EPG5):c.5869+1G>A

gnomAD frequency: 0.00001  dbSNP: rs748670315

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568176	SCV003442533	pathogenic	Vici syndrome	2023-07-17	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 33 of the EPG5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EPG5 are known to be pathogenic (PMID: 23222957, 23674064). This variant is present in population databases (rs748670315, gnomAD 0.0009%). Disruption of this splice site has been observed in individuals with Vici syndrome (PMID: 26917586, 28939701). ClinVar contains an entry for this variant (Variation ID: 1175160). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001530116	SCV005325546	pathogenic	not provided	2024-02-24	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26917586, 28939701, 27694994)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001530116	SCV001744769	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001530116	SCV001957973	likely pathogenic	not provided		no assertion criteria provided	clinical testing