The hospital Israelita Albert Einstein standards for constitutional sequence variants classification: version 2023

• Published in: Human genomics Vol. 17; no. 1; pp. 1 - 15
• Main Authors: Quaio, Caio Robledo D’Angioli Costa, Ceroni, José Ricardo Magliocco, Pereira, Michele Araújo, Teixeira, Anne Caroline Barbosa, Yamada, Renata Yoshiko, Cintra, Vivian Pedigone, Perrone, Eduardo, De França, Marina, Chen, Kelin, Minillo, Renata Moldenhauer, Biondo, Cheysa Arielly, de Mello, Mariana Rezende Bandeira, Moura, Lais Rodrigues, do Nascimento, Amanda Thamires Batista, de Oliveira Pelegrino, Karla, de Lima, Larissa Barbosa, do Amaral Virmond, Luiza, Moreno, Carolina Araujo, Prota, Joana Rosa Marques, de Araujo Espolaor, Jessica Grasiela, Silva, Thiago Yoshinaga Tonholo, Moraes, Gabriel Hideki Izuka, de Oliveira, Gustavo Santos, Moura, Livia Maria Silva, Caraciolo, Marcel Pinheiro, Guedes, Rafael Lucas Muniz, Gretschischkin, Michel Chieregato, Chazanas, Pedro Lui Nigro, Nakamura, Carolina Naomi Izo, de Souza Reis, Rodrigo, Toledo, Carmen Melo, Lage, Fernanda Stussi Duarte, de Almeida, Giovanna Bloise, do Nascimento Júnior, José Bandeira, Cardoso, Milena Andreuzo, de Paula Azevedo, Victor, de Almeida, Tatiana Ferreira, Cervato, Murilo Castro, de Oliveira Filho, Joao Bosco
• Format: Journal Article
• Language: English
• Published: London BioMed Central 16-11-2023; BMC
• Subjects: Associations; Bayesian analysis; Bioinformatics; Brazil; Cancer; Classification; Conserved sequence; Digital archives; Disease; Genes; Genetic disorders; Genetic testing; Genetics; Genomes; Genomics; Guideline; Hospitals; Next-generation sequencing; Nomenclature; Sequence variant; Validity; Variant classification
• DOI: 10.1186/s40246-023-00549-6
• EISSN: 1479-7364
• ISSN: 1479-7364; 1473-9542

BackgroundNext-generation sequencing has had a significant impact on genetic disease diagnosis, but the interpretation of the vast amount of genomic data it generates can be challenging. To address this, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology have established guidelines for standardized variant interpretation. In this manuscript, we present the updated Hospital Israelita Albert Einstein Standards for Constitutional Sequence Variants Classification, incorporating modifications from leading genetics societies and the ClinGen initiative.ResultsFirst, we standardized the scientific publications, documents, and other reliable sources for this document to ensure an evidence-based approach. Next, we defined the databases that would provide variant information for the classification process, established the terminology for molecular findings, set standards for disease-gene associations, and determined the nomenclature for classification criteria. Subsequently, we defined the general rules for variant classification and the Bayesian statistical reasoning principles to enhance this process. We also defined bioinformatics standards for automated classification. Our workgroup adhered to gene-specific rules and workflows curated by the ClinGen Variant Curation Expert Panels whenever available. Additionally, a distinct set of specifications for criteria modulation was created for cancer genes, recognizing their unique characteristics.ConclusionsThe development of an internal consensus and standards for constitutional sequence variant classification, specifically adapted to the Brazilian population, further contributes to the continuous refinement of variant classification practices. The aim of these efforts from the workgroup is to enhance the reliability and uniformity of variant classification.