Submissions for variant NM_152564.5(VPS13B):c.11746-1G>A

gnomAD frequency: 0.00001  dbSNP: rs372327659

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000668082	SCV000792627	likely pathogenic	Cohen syndrome	2017-07-05	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003237983	SCV002011571	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000668082	SCV003454250	pathogenic	Cohen syndrome	2023-08-30	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 552760). Disruption of this splice site has been observed in individual(s) with clinical features of Cohen syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs372327659, gnomAD 0.002%). This sequence change affects an acceptor splice site in intron 61 of the VPS13B gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000668082	SCV004032455	likely pathogenic	Cohen syndrome	2023-05-26	criteria provided, single submitter	clinical testing