In 2009, Illumina released its first whole genome sequencers that were approved for clinical as opposed to research-only use and doctors at academic medical centers began quietly using them to try to diagnose what was wrong with people whom standard approaches had failed to help. In 2009, a team from Stanford led by Euan Ashley performed clinical interpretation of a full human genome, that of bioengineer Stephen Quake. In 2010, Ashley's team reported whole genome molecular autopsy and in 2011, extended the interpretation framework to a fully sequenced family, the West family, who were the first family to be sequenced on the Illumina platform. The price to sequence a genome at that time was $19,500USD, which was billed to the patient but usually paid for out of a research grant; one person at that time had applied for reimbursement from their insurance company.  For example, one child had needed around 100 surgeries by the time he was three years old, and his doctor turned to whole genome sequencing to determine the problem; it took a team of around 30 people that included 12 bioinformatics experts, three sequencing technicians, five physicians, two genetic counsellors and two ethicists to identify a rare mutation in the XIAP that was causing widespread problems.
Due to recent cost reductions (see above) whole genome sequencing has become a realistic application in DNA diagnostics. In 2013, the 3Gb-TEST consortium obtained funding from the European Union to prepare the health care system for these innovations in DNA diagnostics. Quality assessment schemes, Health technology assessment and guidelines have to be in place. The 3Gb-TEST consortium has identified the analysis and interpretation of sequence data as the most complicated step in the diagnostic process. At the Consortium meeting in Athens in September 2014, the Consortium coined the word genotranslation for this crucial step. This step leads to a so-called genoreport. Guidelines are needed to determine the required content of these reports.
Genomes2People (G2P), an initiative of Brigham and Womens Hospital and Harvard Medical School was created in 2011 to examine the integration of genomic sequencing into clinical care of adults and children. G2Ps director, Robert C. Green, had previously led the REVEAL study — Risk EValuation and Education for Alzheimers Disease – a series of clinical trials exploring patient reactions to the knowledge of their genetic risk for Alzheimers. 
In 2018, researchers at Rady Childrens Hospital Institute for Genomic Medicine in San Diego determined that rapid whole-genome sequencing (rWGS) could diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. In a retrospective cohort study of acutely ill inpatient infants in a regional childrens hospital from July 2016-March 2017, forty-two families received rWGS for etiologic diagnosis of genetic disorders. The diagnostic sensitivity of rWGS was 43% (eighteen of 42 infants) and 10% (four of 42 infants) for standard genetic tests (P = .0005). The rate of clinical utility of rWGS (31%, thirteen of 42 infants) was significantly greater than for standard genetic tests (2%, one of 42; P = .0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had a 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800,000-$2,000,000. The findings replicated a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrated improved outcomes, net healthcare savings and consideration as a first tier test in this setting.
A 2018 review of 36 publications found the cost for whole genome sequencing to range from $1,906USD to $24,810USD and have a wide variance in diagnostic yield from 17% to 73% depending on patient groups.