Submissions for variant NM_015378.4(VPS13D):c.10917+4A>G

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002579995	SCV002932911	uncertain significance	not provided	2022-08-04	criteria provided, single submitter	clinical testing	This sequence change falls in intron 55 of the VPS13D gene. It does not directly change the encoded amino acid sequence of the VPS13D protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VPS13D-related conditions. 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 may disrupt the consensus splice site. 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.
Ambry Genetics	RCV002572689	SCV003578631	uncertain significance	Inborn genetic diseases	2021-10-20	criteria provided, single submitter	clinical testing	The c.10917+4A>G intronic alteration consists of a A to G substitution 4 nucleotides after exon 55 (coding exon 54) of the VPS13D gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003926412	SCV004743028	likely benign	VPS13D-related disorder	2019-12-09	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).