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The cost and diagnostic yield of exome sequencing for children with suspected genetic disorders: a benchmarking study



This study aimed to generate benchmark estimates for the cost, diagnostic yield, and cost per positive diagnosis of diagnostic exome sequencing (ES) in heterogeneous pediatric patient populations and to illustrate how the design of an ES service can influence its cost and yield.


A literature review and Monte Carlo simulations were used to generate benchmark estimates for singleton and trio ES. A cost model for the Clinical Assessment of the Utility of Sequencing and Evaluation as a Service (CAUSES) study, which is testing a proposed delivery model for diagnostic ES in British Columbia, is used to illustrate the potential effects of changing the service design.


The benchmark diagnostic yield was 34.3% (95% confidence interval (CI): 23.2–46.5) for trio ES and 26.5% (95% CI: 12.9–42.9) for singleton ES. The benchmark cost of delivery was C$6,437 (95% CI: $5,305–$7,704) in 2016 Canadian dollars (US$4,859; 4,391€) for trio ES and C$2,576 (95% CI: $1,993–$3,270) (US$1,944; 1,757€) for singleton ES. Scenario models for CAUSES suggest that alternative service designs could reduce costs but might lead to a higher cost per diagnosis due to lower yields.


Broad conclusions about the cost-effectiveness of ES should be drawn with caution when relying on studies that use cost or yield assumptions that lie at the extremes of the benchmark ranges.

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The authors declare no conflict of interest.


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The CAUSES Clinic is made possible by a $3 million commitment from Mining for Miracles through BC Children’s Hospital Foundation and is supported by Genome British Columbia, the Provincial Health Services Authority, BC Children’s and Women’s Hospitals, the Provincial Medical Genetics Program, BC Children’s Hospital Pathology and Laboratory Medicine, and the University of British Columbia. Clerical and administrative support for the Genomic Consultation Service is provided by the Provincial Medical Genetics Program, BC Women’s Hospital. This study was also supported by the Canadian Institutes of Health Research Emerging Team for Rare Diseases grant (funding reference number 119193). The CAUSES Clinic thanks the patients and their families for their participation.

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The authors declare no conflict of interest.

Correspondence to Larry D Lynd PhD.

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  • cost
  • cost-effectiveness
  • diagnostic yield
  • exome sequencing
  • pediatric patients

Further reading

Figure 1: The eight steps involved in the CAUSES study’s diagnostic ES service workflow, with figures indicating the actual number of families who were processed through each step of the workflow in 2016.