Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Rady Children's Institute for Genomic Medicine, |
RCV000023825 | SCV000996177 | pathogenic | Joubert syndrome 15 | 2018-07-23 | criteria provided, single submitter | clinical testing | This variant affects the canonical splice acceptor site of intron 6 and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has been previously reported as a homozygous change in a patient with Joubert Syndrome (PMID: 22246503). It is present in the heterozygous state in the gnomAD population database at 0.0008% (2/246208) and thus is presumed to be rare. In silico analyses support a deleterious effect of the c.423-2A>C variant on protein function. Based on the available evidence, the c.423-2A>C variant is classified as pathogenic. |
| Invitae | RCV000023825 | SCV001587214 | pathogenic | Joubert syndrome 15 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 6 of the CEP41 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 CEP41 are known to be pathogenic (PMID: 22246503). This variant is present in population databases (rs781815473, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with Joubert syndrome (PMID: 22246503). ClinVar contains an entry for this variant (Variation ID: 30840). 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. |
| OMIM | RCV000023825 | SCV000045116 | pathogenic | Joubert syndrome 15 | 2012-01-15 | no assertion criteria provided | literature only |