ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.8516C>T (p.Pro2839Leu) (rs147426388)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000646708 SCV000895704 uncertain significance Orofaciodigital syndrome 6; Joubert syndrome 17 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000419680 SCV000534820 uncertain significance not provided 2018-08-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the C5orf42 gene. The P2839L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 8/9894 (0.08%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). The P2839L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000382022 SCV000457343 uncertain significance Joubert syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000646708 SCV000768487 uncertain significance Orofaciodigital syndrome 6; Joubert syndrome 17 2018-10-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2839 of the C5orf42 protein (p.Pro2839Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs147426388, ExAC 0.06%). This variant has not been reported in the literature in individuals with C5orf42-related disease. ClinVar contains an entry for this variant (Variation ID: 353421). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.