ClinVar Miner

Submissions for variant NM_001384732.1(CPLANE1):c.5348C>A (p.Ala1783Asp)

gnomAD frequency: 0.00002  dbSNP: rs200444162
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics, University of Zurich RCV000611750 SCV000579468 likely pathogenic Joubert syndrome 17 2017-05-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001226490 SCV001398805 pathogenic not provided 2023-12-17 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1783 of the CPLANE1 protein (p.Ala1783Asp). This variant is present in population databases (rs200444162, gnomAD 0.003%). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 25920555, 29321670). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 427895). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CPLANE1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002475966 SCV002791207 likely pathogenic Orofaciodigital syndrome type 6; Joubert syndrome 17 2022-01-28 criteria provided, single submitter clinical testing
GeneDx RCV001226490 SCV003806133 likely pathogenic not provided 2022-10-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25407461, 25920555, 29321670)
Ambry Genetics RCV004023274 SCV004850605 likely pathogenic Inborn genetic diseases 2020-11-18 criteria provided, single submitter clinical testing The c.5348C>A (p.A1783D) alteration is located in exon 26 (coding exon 25) of the C5orf42 gene. This alteration results from a C to A substitution at nucleotide position 5348, causing the alanine (A) at amino acid position 1783 to be replaced by an aspartic acid (D). Based on data from the Genome Aggregation Database (gnomAD) database, the C5orf42 c.5348C>A alteration was observed in 0.0012% (3/250642) of total alleles studied, with a frequency of 0.0026% (3/113428) in the European (non-Finnish) subpopulation. This alteration has been detected in the compound heterozygous state in multiple individuals with features of Joubert syndrome (Asadollahi, 2018; Fleming, 2017). This amino acid position is highly conserved in available vertebrate species. The in silico prediction for the p.A1783D alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.