Structural and Non-Coding Variants Increase the Diagnostic Yield of Clinical Whole Genome Sequencing for Rare Diseases

Although whole genome sequencing is increasingly used for the diagnosis of patients with rare disease, diagnostic yields often disappointingly low. We undertook WGS on a cohort of 122 unrelated RD patients and applied a bioinformatics pipeline that would allow an in-depth interrogation of the genome to provide a comprehensive analysis of all variant types. Our results demonstrate that structural, splice-site and intronic variants make a substantial contribution to diagnostic yield and therefore that comprehensive analysis of the entire genome is essential to maximise the value of clinical WGS.EGA study EGAS00001007575