ClinVar Miner

Submissions for variant NM_001080522.2(CC2D2A):c.4552C>T (p.Arg1518Trp)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703032 SCV000831912 uncertain significance Joubert syndrome; Meckel-Gruber syndrome 2017-09-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1518 of the CC2D2A protein (p.Arg1518Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs767260373, ExAC 0.002%). This variant has been reported in the homozygous state in individuals affected with Joubert syndrome (PMID: 23692786). 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: "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.
Broad Institute Rare Disease Group,Broad Institute RCV000984486 SCV001132534 uncertain significance Joubert syndrome 9 2018-11-15 criteria provided, single submitter research The homozygous p.Arg1518Trp variant in CC2D2A was identified by our study in one individual with Joubert Syndrome. This variant has been identified in <0.01% (1/110440) of European (Non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs767260373). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg1518Trp variant is uncertain.

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