ClinVar Miner

Submissions for variant NM_001080522.2(CC2D2A):c.2326G>A (p.Gly776Arg) (rs200764366)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726192 SCV000342757 uncertain significance not provided 2017-06-28 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765757 SCV000897145 uncertain significance COACH syndrome; Meckel syndrome type 6; Joubert syndrome 9 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000726192 SCV000329212 uncertain significance not provided 2016-12-14 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CC2D2A gene. The G776R variant has been reported previously in an individual with anophthalmia, microphthalmia, or coloboma (Deml et al., 2016). The G776R variant is observed in 99/66,500 (0.15%) alleles from individuals of European (Non-Finnish) background and in 8/6,606 (0.12%) alleles from individuals of European (Finnish) background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G776R 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, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CC2D2A-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000232423 SCV000285830 uncertain significance Joubert syndrome; Meckel-Gruber syndrome 2016-11-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 776 of the CC2D2A protein (p.Gly776Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs200764366, ExAC 0.1%). This variant has been reported in an individual affected with anophthalmia / microphthalmia (PMID: 26130484). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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