ClinVar Miner

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

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Total submissions: 4
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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.
