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Publications

Journal Article Epublish 2 citations

PubMed: 40332002 DOI: 10.3390/ijms26083509

Medically Actionable Secondary Findings from Whole-Exome Sequencing (WES) Data in a Sample of 3972 Individuals.

Int J Mol Sci 26(8)

Authors: Mafalda Melo, Mariana Ribeiro, Paulo Filipe Silva, Susana Valente, Filipe Alves, Margarida Venâncio, Jorge Sequeiros, João Parente Freixo, Diana Antunes, Jorge Oliveira

Affiliations

  • Medical Genetics Unit, Hospital Dona Estefânia, Unidade Local de Saúde de Sao José, 1169-045 Lisbon, Portugal.
  • Centre for Predictive and Preventive Genetics, Institute for Molecular and Cell Biology (CGPP-IBMC), 4200-135 Porto, Portugal.
  • Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal.
  • Centre for Predictive and Preventive Genetics, Institute for Molecular and Cell Biology (CGPP-IBMC), 4200-135 Porto, Portugal. Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal.
  • ICBAS School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal.
  • Unit for Multidisciplinary Research in Biomedicine (UMIB), ICBAS/ITR-Laboratory for Integrative and Translational Research in Population Health, University of Porto, 4050-313 Porto, Portugal.
  • NOVA National School of Public Health (ENSP), NOVA University Lisbon, 1600-560 Lisbon, Portugal.
  • Centre for Predictive and Preventive Genetics, Institute for Molecular and Cell Biology (CGPP-IBMC), 4200-135 Porto, Portugal. Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal. ICBAS School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal. Unit for Multidisciplinary Research in Biomedicine (UMIB), ICBAS/ITR-Laboratory for Integrative and Translational Research in Population Health, University of Porto, 4050-313 Porto, Portugal.

Abstract

The application of whole-exome sequencing (WES) for diagnostic purposes has the potential to unravel secondary findings unrelated with the primary reason of testing. Some of those might be of high clinical utility and comprise disease-causing variants in genes, related to life-threatening and clinically actionable diseases. Clarifying the allelic frequencies of such variants in specific populations is a crucial step for the large-scale deployment of genomic medicine. We analysed medically relevant variants in the 81 genes from the American College of Medical Genetics and Genomics (ACMG) v3.2 list of actionable loci, using WES data from a diagnostic laboratory cohort of 3972 persons, tentatively resampled to represent the Portuguese population geographic distribution. We identified medically actionable variants in 6.2% of our cohort, distributed across several disease domains: cardiovascular disorders (3.0%), cancer predisposition (2.0%), miscellaneous disorders (1.1%), and metabolic disorders (0.1%). Additionally, we estimated a frequency of heterozygotes for recessive disease alleles of 11.1%. Overall, our results suggest that medically actionable findings can be identified in approximately 6.2% of persons from our population. This is the first study estimating medically actionable findings in Portugal. These results provide valuable insight for patients, healthcare providers, and policymakers involved in advancing genomic medicine at the national and international level.

MeSH

Genes, Exome, Exome Sequencing, Genomic Medicine