ClinVar Miner

Submissions for variant NM_023073.3(CPLANE1):c.6158T>A (p.Phe2053Tyr) (rs189493985)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000417648 SCV000536314 uncertain significance not provided 2017-01-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the C5orf42 gene. The F2053Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The F2053Y variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The F2053Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000706312 SCV000835354 uncertain significance Orofaciodigital syndrome 6; Joubert syndrome 17 2018-10-09 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with tyrosine at codon 2053 of the C5orf42 protein (p.Phe2053Tyr). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and tyrosine. This variant is present in population databases (rs189493985, ExAC 0.02%). This variant has not been reported in the literature in individuals with C5orf42-related disease. ClinVar contains an entry for this variant (Variation ID: 392966). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably 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.

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