Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002021487 | SCV002312209 | likely pathogenic | Cohen syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 5 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). 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. 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: 1518080). This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. |
Centro Nacional de Genética Medica "Dr. |
RCV002021487 | SCV005908048 | pathogenic | Cohen syndrome | 2024-08-01 | criteria provided, single submitter | research | The c.580+1G>A, variant found is located in exon 5 of the VPS13B gene. The variant found in the VPS13B gene is reported in ClinVar (RCV002021487) in a patient with Cohen's syndrome and classified as pathogenic. Loss-of-function variants are a common pathogenic mechanism in the VPS13B gene (PVS1). The variant found is found at very low frequency in population databases such as GnomAD, ExAc, or 1000 Genomes (PM2_Supporting). |