Diagnostic gene sequencing panels: from design to report—a technical standard of the American College of Medical Genetics and Genomics (ACMG)

Abstract

Gene sequencing panels are a powerful diagnostic tool for many clinicalpresentations associated with genetic disorders. Advances in DNA sequencingtechnology have made gene panels more economical, flexible, and efficient. Becausethe genes included on gene panels vary widely between laboratories in gene content(e.g., number, reason for inclusion, evidence level for gene–disease association)and technical completeness (e.g., depth of coverage), standards that addresstechnical and clinical aspects of gene panels are needed. This document serves as atechnical standard for laboratories designing, offering, and reporting gene paneltesting. Although these principles can apply to multiple indications for genetictesting, the primary focus is on diagnostic gene panels (as opposed to carrierscreening or predictive testing) with emphasis on technical considerations for thespecific genes being tested. This technical standard specifically addresses theimpact of gene panel content on clinical sensitivity, specificity, and validity—inthe context of gene evidence for contribution to and strength of evidence forgene–disease association—as well as technical considerations such as sequencinglimitations, presence of pseudogenes/gene families, mosaicism, transcript choice,detection of copy-number variants, reporting, and disclosure of assaylimitations.