Submissions for variant NM_152564.5(VPS13B):c.8098-1G>C

dbSNP: rs1554565484

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000498849	SCV000589823	likely pathogenic	not provided	2016-04-06	criteria provided, single submitter	clinical testing	The c.8173-1G>C variant in the VPS13B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 44. It is predicted to cause abnormal gene splicing resulting in an in-frame protein product with an abnormal message. However, in the absence of RNA/functional studies, the actual effect of c.8173-1G>C in this individual is unknown. The c.8173-1G>C variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.8173-1G>C variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000668997	SCV001214724	likely pathogenic	Cohen syndrome	2024-03-28	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 44 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of VPS13B-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 432136). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV000668997	SCV005416257	likely pathogenic	Cohen syndrome		criteria provided, single submitter	clinical testing	PVS1_Moderate+PM2_Supporting+PM3+PP4
Fulgent Genetics, Fulgent Genetics	RCV000668997	SCV005667396	likely pathogenic	Cohen syndrome	2024-01-05	criteria provided, single submitter	clinical testing
Counsyl	RCV000668997	SCV000793691	likely pathogenic	Cohen syndrome	2019-07-12	no assertion criteria provided	clinical testing