Human Genomics (Nov 2023)

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

  • Caio Robledo D’Angioli Costa Quaio,
  • José Ricardo Magliocco Ceroni,
  • Michele Araújo Pereira,
  • Anne Caroline Barbosa Teixeira,
  • Renata Yoshiko Yamada,
  • Vivian Pedigone Cintra,
  • Eduardo Perrone,
  • Marina De França,
  • Kelin Chen,
  • Renata Moldenhauer Minillo,
  • Cheysa Arielly Biondo,
  • Mariana Rezende Bandeira de Mello,
  • Lais Rodrigues Moura,
  • Amanda Thamires Batista do Nascimento,
  • Karla de Oliveira Pelegrino,
  • Larissa Barbosa de Lima,
  • Luiza do Amaral Virmond,
  • Carolina Araujo Moreno,
  • Joana Rosa Marques Prota,
  • Jessica Grasiela de Araujo Espolaor,
  • Thiago Yoshinaga Tonholo Silva,
  • Gabriel Hideki Izuka Moraes,
  • Gustavo Santos de Oliveira,
  • Livia Maria Silva Moura,
  • Marcel Pinheiro Caraciolo,
  • Rafael Lucas Muniz Guedes,
  • Michel Chieregato Gretschischkin,
  • Pedro Lui Nigro Chazanas,
  • Carolina Naomi Izo Nakamura,
  • Rodrigo de Souza Reis,
  • Carmen Melo Toledo,
  • Fernanda Stussi Duarte Lage,
  • Giovanna Bloise de Almeida,
  • José Bandeira do Nascimento Júnior,
  • Milena Andreuzo Cardoso,
  • Victor de Paula Azevedo,
  • Tatiana Ferreira de Almeida,
  • Murilo Castro Cervato,
  • Joao Bosco de Oliveira Filho

DOI
https://doi.org/10.1186/s40246-023-00549-6
Journal volume & issue
Vol. 17, no. 1
pp. 1 – 15

Abstract

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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.

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