Best practices for the interpretation and reporting of clinical genome sequencing

Genome sequencing (GS) exhibits high analytical performance and shows promise as a first-tier diagnostic test for patients with rare genetic disorders. Compared to exome sequencing (ES) and other molecular diagnostic tests (e.g. sequencing panels, microarrays), GS is more comprehensive for two reasons: (i) it allows detection of a broader range of variant types in a single assay, including single nucleotide variants (SNV), small insertions and deletions, mitochondrial variants (MT), repeat expansions (RE), copy number variants (CNV) and other structural variants (SV); and (ii) it is untargeted, resulting in more uniform coverage of exonic regions and added coverage of intronic, intergenic and regulatory regions.