Submissions for variant NM_152564.5(VPS13B):c.2651-1G>A

dbSNP: rs386834077

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000050066	SCV003440655	pathogenic	Cohen syndrome	2022-06-14	criteria provided, single submitter	clinical testing	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. ClinVar contains an entry for this variant (Variation ID: 56653). Disruption of this splice site has been observed in individual(s) with Cohen syndrome (PMID: 19006247). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 18 of the VPS13B 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 VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111).
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	RCV000050066	SCV000082475	probable-pathogenic	Cohen syndrome		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.