ClinVar Miner

Submissions for variant NM_018718.3(CEP41):c.423-2A>C (rs781815473)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego 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 2020-10-08 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 and likely results in an absent or disrupted protein product. This variant is present in population databases (rs781815473, ExAC 0.001%). This variant 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, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CEP41 are known to be pathogenic (PMID: 22246503). 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

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