C2CD3 was first reported in relation to autosomal recessive orofaciodigital syndrome XIV in 2014 (PMID: 24997988). There's only one disease assertion made for C2CD3, therefore a standard curation was completed. Within humans, at least 14 unique variants (deletion, duplication, indel, insertion, single nucleotide) have been reported and more evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) was reached. The mechanism of pathogenicity is reported to be loss of function whereby biallelic pathogenic variants in the C2CD3 gene lead to shortening of centrioles and lack of ciliogenesis initiation regulation through centriolar maturation, ciliogenesis protein recruitment, and ciliary vesicle docking. This gene-disease relationship is also supported by animal models (mouse and chick), functional alterations (patient cells), and protein interaction evidence (PMID: 19004860,25053433,27094867,24997988). In summary, there is “Definitive” evidence supporting the relationship between C2CD3 as an AR Ciliopathy. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Kidney Cystic and Ciliopathy Disorders GCEP on the meeting date May 24, 2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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