1. The hospital Israelita Albert Einstein standards for constitutional sequence variants classification: version 2023.
- Author
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Quaio CRDC, Ceroni JRM, Pereira MA, Teixeira ACB, Yamada RY, Cintra VP, Perrone E, De França M, Chen K, Minillo RM, Biondo CA, de Mello MRB, Moura LR, do Nascimento ATB, de Oliveira Pelegrino K, de Lima LB, do Amaral Virmond L, Moreno CA, Prota JRM, de Araujo Espolaor JG, Silva TYT, Moraes GHI, de Oliveira GS, Moura LMS, Caraciolo MP, Guedes RLM, Gretschischkin MC, Chazanas PLN, Nakamura CNI, de Souza Reis R, Toledo CM, Lage FSD, de Almeida GB, do Nascimento Júnior JB, Cardoso MA, de Paula Azevedo V, de Almeida TF, Cervato MC, and de Oliveira Filho JB
- Subjects
- Humans, United States, Mutation, Reproducibility of Results, Bayes Theorem, Genome, Human, Genetic Variation, Genetic Testing
- Abstract
Background: Next-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., Results: First, 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., Conclusions: The 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., (© 2023. The Author(s).)
- Published
- 2023
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