Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001220865 | SCV001392877 | pathogenic | Developmental and epileptic encephalopathy, 1; Autosomal recessive spinocerebellar ataxia 12 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 6 of the WWOX 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 WWOX are known to be pathogenic (PMID: 24456803, 25411445). This variant is present in population databases (rs730882215, gnomAD 0.0009%). Disruption of this splice site has been observed in individuals with clinical features of WWOX-related conditions (PMID: 27717089, 29852413). ClinVar contains an entry for this variant (Variation ID: 183303). 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. |
Gene |
RCV001558644 | SCV001780638 | pathogenic | not provided | 2021-12-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Canonical splice site variant predicted to result in an in-frame deletion of a critical region; This variant is associated with the following publications: (PMID: 27717089, 29852413, 30361190, 25558065, 26345274, 32552793, 25411445) |
Pathology and Clinical Laboratory Medicine, |
RCV000408849 | SCV002073820 | pathogenic | Developmental and epileptic encephalopathy, 28 | criteria provided, single submitter | clinical testing | ||
Preventiongenetics, |
RCV003398828 | SCV004111354 | pathogenic | WWOX-related condition | 2022-12-20 | criteria provided, single submitter | clinical testing | The WWOX c.606-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant was reported as pathogenic for developmental and epileptic encephalopathy (Table S1, Alazami et al. 2015. PubMed ID: 25558065; Table S3, Alabdullatif et al. 2016. PubMed ID: 27717089; Kothur et al. 2018. PubMed ID: 29852413). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-78458766-G-A). Variants that disrupt the consensus splice acceptor site in WWOX are expected to be pathogenic. This variant is interpreted as pathogenic. |
Department Of Translational Genomics |
RCV000162124 | SCV000196409 | likely pathogenic | Global developmental delay; Abnormal facial shape; Brain atrophy | 2014-12-01 | no assertion criteria provided | research | |
Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV000408849 | SCV000484928 | likely pathogenic | Developmental and epileptic encephalopathy, 28 | no assertion criteria provided | clinical testing |