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The molecular basis for this phenotypical variability is not understood but basal exon skipping likely contributes to tolerance for deleterious mutations via tissue\u2010specific preservation of the amount of expressed functional protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We systematically reviewed and annotated genetic variants and clinical presentations reported in <jats:italic>CEP120<\/jats:italic>\u2010 and <jats:italic>CC2D2A<\/jats:italic>\u2010associated disease and we combined <jats:italic>in silico<\/jats:italic> and <jats:italic>ex vivo<\/jats:italic> approaches to study tissue\u2010specific transcripts and identify molecular targets for exon skipping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We confirmed more severe clinical presentations associated with truncating <jats:italic>CC2D2A<\/jats:italic> mutations. We identified and confirmed basal exon skipping in the kidney, with possible relevance for organ\u2010specific disease manifestations. Finally, we proposed a multimodal approach to classify exons amenable to exon skipping. By mapping reported variants, 14 truncating mutations in 7 <jats:italic>CC2D2A<\/jats:italic> exons were identified as potentially rescuable by targeted exon skipping, an approach that is already in clinical use for other inherited human diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genotype\u2010phenotype correlations for <jats:italic>CC2D2A<\/jats:italic> support the deleteriousness of null alleles and <jats:italic>CC2D2A<\/jats:italic>, but not <jats:italic>CEP120<\/jats:italic>, offers potential for therapeutic exon skipping approaches.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1603","type":"journal-article","created":{"date-parts":[[2021,1,24]],"date-time":"2021-01-24T08:35:05Z","timestamp":1611477305000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Update of genetic variants in <i>CEP120<\/i> and <i>CC2D2A<\/i>\u2014With an emphasis on genotype\u2010phenotype correlations, tissue specific transcripts and exploring mutation specific exon skipping therapies"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8245-1929","authenticated-orcid":false,"given":"Miguel","family":"Barroso\u2010Gil","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1178-7980","authenticated-orcid":false,"given":"Eric","family":"Olinger","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Faculty of Medical Sciences Newcastle University Newcastle Upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8531-1534","authenticated-orcid":false,"given":"Simon A.","family":"Ramsbottom","sequence":"additional","affiliation":[{"name":"Translational 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