Abstract
Although NGS technologies are well-embedded in the clinical setting for identification of genetic causes of disease, guidelines issued by professional bodies are inconsistent regarding some aspects of reporting results. Most recommendations do not give detailed guidance about whether variants of uncertain significance (VUS) should be reported by laboratory personnel to clinicians, and give conflicting messages regarding whether unsolicited findings (UF) should be reported. There are also differences both in their recommendations regarding whether actively searching for secondary findings (SF) is appropriate, and in the extent to which they address the duty (or lack thereof) to reanalyse variants when new information arises. An interdisciplinary working group considered the current guidelines, their own experiences, and data from a recent qualitative study to develop a set of points to consider for laboratories reporting results from diagnostic NGS. These points to consider fall under six categories: (i) Testing approaches and technologies used, (ii) Approaches for VUS; (iii) Approaches for reporting UF, (iv) Approaches regarding SF; (v) Reanalysis of data & re-contact; and vi) Minors. While it is unclear whether uniformity in reporting across all laboratories is desirable, we hope these points to consider will be useful to diagnostic laboratories as they develop their processes for making decisions about reporting VUS and UF from NGS in the diagnostic context.
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References
Boycott K, Hartley T, Adam S, et al The clinical application of genome-wide sequencing for monogenic diseases in Canada: Position Statement of the Canadian College of Medical Geneticists. J Med Genet 2015;52:431–7.
Matthijs G, Souche E, Alders M, et al Guidelines for diagnostic next-generation sequencing. Eur J Hum Genet 2016;24:1515.
van El CG, Cornel MC, Borry P, et al Whole-genome sequencing in health care: Recommendations of the European Society of Human Genetics. Eur J Hum Genet 2013;21:S1–S5.
Kalia SS, Adelman K, Bale SJ, et al Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SFv2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med 2016;19:249–55.
Green RC, Berg JS, Grody MWW, et al ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 2013;15:565–74.
Vears DF, Sénécal K, Borry P. Reporting practices for unsolicited and secondary findings from next generation sequencing technologies: Perspectives of laboratory personnel. Hum Mutat 2017;38:905–11.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405–24.
Weiss MM, Van der Zwaag B, Jongbloed J, et al Best practice guidelines for the use of next-generation sequencing applications in genome diagnostics: A national collaborative study of Dutch genome diagnostic laboratories. Hum Mutat 2013;34:1313–21.
Lu JT, Campeau PM, Lee BH. Genotype-phenotype correlation-promiscuity in the era of next generation sequencing. New Engl J Med 2014;371:591–3.
Fiore RN, Goodman KW. Precision medicine ethics: selected issues and developments in next-generation sequencing, clinical oncology, and ethics. Curr Opin Oncol 2016;28:83–87.
Christenhusz GM, Devriendt K, Dierickx K. Secondary variants--in defense of a more fitting term in the incidental findings debate. Eur J Hum Genet 2013;21:1331–4.
Tan N, Amendola LM, O’Daniel JM, et al Is “incidental finding” the best term?: a study of patients’ preferences. Genet Med 2017;19:176–81.
Dheensa S, Shkedi-Rafid S, Crawford G, Bertier G, Schonstein L, Lucassen A: Mangement of incidental findings in clinical genomic sequencing: eLS. Chichester: John Wiley & Sons Ltd., 2016.
European Council: Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine. Oviedo: 1997.
World Medical Association: Declaration of Lisbon on the Rights of the Patient. Adopted by the 34th World Medical Assembly, Lisbon, Portugal, and reaffirmed by the 200th WMA Council Session, Oslo, Norway, 2015]: 1981 [amended by the 47th WMA General Assembly, Bali, Indonesia, 1995; editorially revised by the 171st WMA Council Session, Santiago, Chile, 2005.
Wilson J, Jungner G: Principles and practice of screening for disease. Geneva: World Health Organization, 1968.
Hart JT. The inverse care law. Lancet 1971;297:405–12.
Sénécal K, Vears DF, Bertier G, Knoppers BM, Borry P. Genome-based newborn screening: a conceptual analysis of the best interests of the child standard. Personal Med 2015;12:439–41.
European Union: Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation). 2016.
Danya F. Vears, Karine Sénécal, Pascal Borry, (2017) Reporting practices for variants of uncertain significance from next generation sequencing technologies. European Journal of Medical Genetics 60 (10):553–558
Acknowledgements
We acknowledge the support of the Research Fund Flanders (Belgium) and the Ministère de l’Économie, de la Science et de l’Innovation du Québec, PSR-SIIRI-850 (Canada). We also thank Prof François Rousseau, Université Laval, Quebec for his participation in the working group.
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Vears, D.F., Sénécal, K., Clarke, A.J. et al. Points to consider for laboratories reporting results from diagnostic genomic sequencing. Eur J Hum Genet 26, 36–43 (2018). https://doi.org/10.1038/s41431-017-0043-9
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DOI: https://doi.org/10.1038/s41431-017-0043-9
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