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There are around 200 known ciliopathy disease genes and whilst genetic testing can provide an accurate diagnosis, 24\u201360% of ciliopathy patients who undergo genetic testing do not receive a genetic diagnosis. This is partly because following current guidelines from the American College of Medical Genetics and the Association for Molecular Pathology, it is difficult to provide a confident clinical diagnosis of disease caused by missense or non-coding variants, which account for more than one-third of cases of disease. Mutations in\n                    <jats:italic>PRPF31<\/jats:italic>\n                    are the second most common cause of the degenerative retinal ciliopathy autosomal dominant retinitis pigmentosa. Here, we present a high-throughput high-content imaging assay providing quantitative measure of effect of missense variants in\n                    <jats:italic>PRPF31<\/jats:italic>\n                    which meets the recently published criteria for a baseline standard in vitro test for clinical variant interpretation. This assay utilizes a new\n                    <jats:italic>PRPF31<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    human retinal cell line generated using CRISPR gene editing to provide a stable cell line with significantly fewer cilia in which novel missense variants are expressed and characterised. We show that high-content imaging of cells expressing missense variants in a ciliopathy gene on a null background can allow characterisation of variants according to the cilia phenotype. We hope that this will be a useful tool for clinical characterisation of\n                    <jats:italic>PRPF31<\/jats:italic>\n                    variants of uncertain significance, and can be extended to variant classification in other ciliopathies.\n                  <\/jats:p>","DOI":"10.1007\/s00439-020-02228-1","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T09:02:35Z","timestamp":1603443755000},"page":"593-607","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A CRISPR and high-content imaging assay compliant with ACMG\/AMP guidelines for clinical variant interpretation in ciliopathies"],"prefix":"10.1007","volume":"140","author":[{"given":"Liliya","family":"Nazlamova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. 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No patients or patient material were used in this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All genetic variant data were obtained from publicly available database ClinVar. No patients or patient material were used in this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}