Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000522071 | SCV000618118 | pathogenic | not provided | 2016-05-21 | criteria provided, single submitter | clinical testing | The c.11571-2 A>G variant in VPS13B has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. c.11571-2 A>G destroys the canonical splice acceptor site in intron 60. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Neither the frameshift nor splice site variant were observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating these are not common benign variants in these populations. |
| Invitae | RCV000533932 | SCV000630860 | pathogenic | Cohen syndrome | 2019-10-03 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 60 of the VPS13B gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. 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). 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. This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual with clinical features consistent with Cohen syndrome (Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has not been reported in the literature in individuals with VPS13B-related disease. This variant is not present in population databases (ExAC no frequency). |
| Counsyl | RCV000533932 | SCV000788489 | likely pathogenic | Cohen syndrome | 2017-06-15 | criteria provided, single submitter | clinical testing |