Although WGS could arguably offer the most sensitive and comprehensive strategy for detecting germline CPG variants, it is resource intensive in terms of sequencing, data storage, and analytical capacity. In this study, the conservative variant filtering and assessment and the small number of non-coding variants that were used for data interrogation reduced the post-sequencing burden of variants, but small changes to these processes would lead to significant increases with uncertain clinical utility. The approximate cost per sample of WGS as part of the NIHR BioResource Rare Disease project is $1,400, consistent with figures collated by the National Human Genome Research Institute in 2016 and higher than the $1,000 per exome derived from that survey.51 The TCP in our department is currently charged at around $450 per sample. Justification of the extra costs compared with those of other NGS assays, such as panel tests or WES, requires the demonstration that WGS can increase the diagnostic rate over that of other approaches through enhanced detection of coding SNVs and indels, SV identification, or analysis of non-coding regions.