Submissions for variant NM_015378.4(VPS13D):c.6595A>G (p.Ser2199Gly)

gnomAD frequency: 0.00018  dbSNP: rs545160328

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001565634	SCV001789017	uncertain significance	not provided	2020-03-19	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Neuberg Centre For Genomic Medicine, NCGM	RCV004546666	SCV005042855	uncertain significance	Autosomal recessive cerebellar ataxia-saccadic intrusion syndrome		criteria provided, single submitter	clinical testing	The missense variant c.6595A>Gp.Ser2199Gly in VPS13D gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The observed variant has been reported with allele frequency of 0.02% in gnomAD exomes database. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Ser2199Gly in VPS13D is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Ser at position 2199 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance VUS.