Submissions for variant NM_152564.5(VPS13B):c.7247+2T>C

dbSNP: rs1563908020

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000707693	SCV000836800	pathogenic	Cohen syndrome	2018-02-26	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 40 of the VPS13B gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant is reported to be combination with another VPS13B variant in an individual with features consistent with Cohen syndrome (Invitae). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000707693	SCV000893773	likely pathogenic	Cohen syndrome	2018-10-31	criteria provided, single submitter	clinical testing
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV002273824	SCV002558782	not provided	not provided		no assertion provided	research