Diagnostic interpretation of genetic studies in patients with primary immunodeficiency diseases: A working group report of the Primary Immunodeficiency Diseases Committee of the American Academy of Allergy, Asthma & Immunology

• Published in: Journal of allergy and clinical immunology Vol. 145; no. 1; pp. 46 - 69
• Main Authors: Chinn, Ivan K., Chan, Alice Y., Chen, Karin, Chou, Janet, Dorsey, Morna J., Hajjar, Joud, Jongco, Artemio M., Keller, Michael D., Kobrynski, Lisa J., Kumanovics, Attila, Lawrence, Monica G., Leiding, Jennifer W., Lugar, Patricia L., Orange, Jordan S., Patel, Kiran, Platt, Craig D., Puck, Jennifer M., Raje, Nikita, Romberg, Neil, Slack, Maria A., Sullivan, Kathleen E., Tarrant, Teresa K., Torgerson, Troy R., Walter, Jolan E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: Chromosomal microarray; exome sequencing; gene panel; genetic testing; genome sequencing; Mendelian; primary immunodeficiency; Sanger sequencing; variant interpretation; CADD; SIFT; WGS; WES; HPO; CNV; tools; SCID; aCGH; exome sequencing; ExAC; SNP; CMA; TfR1; variant interpretation; primary immunodeficiency; NCBI; Chromosomal microarray; PIDD; SS; Mendelian; CGD; GTEx; ACMG; ESP; AF; ddNTP; OMIM; gnomAD; gene panel; GEO; MAF; VUS; genetic testing; genome sequencing; Sanger sequencing; NGS; TGP; indel
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2019.09.009

Genetic testing has become an integral component of the diagnostic evaluation of patients with suspected primary immunodeficiency diseases. Results of genetic testing can have a profound effect on clinical management decisions. Therefore clinical providers must demonstrate proficiency in interpreting genetic data. Because of the need for increased knowledge regarding this practice, the American Academy of Allergy, Asthma & Immunology Primary Immunodeficiency Diseases Committee established a work group that reviewed and summarized information concerning appropriate methods, tools, and resources for evaluating variants identified by genetic testing. Strengths and limitations of tests frequently ordered by clinicians were examined. Summary statements and tables were then developed to guide the interpretation process. Finally, the need for research and collaboration was emphasized. Greater understanding of these important concepts will improve the diagnosis and management of patients with suspected primary immunodeficiency diseases.