Diagnostic gene sequencing panels: from design to report-a technical standard of the American College of Medical Genetics and Genomics (ACMG).
Document Type
Article
Publication Date
3-2020
Identifier
DOI: 10.1038/s41436-019-0666-z
Abstract
Gene sequencing panels are a powerful diagnostic tool for many clinical presentations associated with genetic disorders. Advances in DNA sequencing technology have made gene panels more economical, flexible, and efficient. Because the 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 address technical and clinical aspects of gene panels are needed. This document serves as a technical standard for laboratories designing, offering, and reporting gene panel testing. Although these principles can apply to multiple indications for genetic testing, the primary focus is on diagnostic gene panels (as opposed to carrier screening or predictive testing) with emphasis on technical considerations for the specific genes being tested. This technical standard specifically addresses the impact of gene panel content on clinical sensitivity, specificity, and validity-in the context of gene evidence for contribution to and strength of evidence for gene-disease association-as well as technical considerations such as sequencing limitations, presence of pseudogenes/gene families, mosaicism, transcript choice, detection of copy-number variants, reporting, and disclosure of assay limitations.
Journal Title
Genetics in medicine : official journal of the American College of Medical Genetics
Volume
22
Issue
3
First Page
453
Last Page
461
MeSH Keywords
Genetic Testing; Genetics, Medical; Genomics; High-Throughput Nucleotide Sequencing; Humans; Laboratories; Molecular Diagnostic Techniques; Mutation; United States
Keywords
design; gene panel sequencing; genetic testing; next-generation sequencing (NGS); technical standard
Recommended Citation
Bean LJH, Funke B, Carlston CM, et al. Diagnostic gene sequencing panels: from design to report-a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2020;22(3):453-461. doi:10.1038/s41436-019-0666-z
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