Analysis of laboratory reporting practices using a quality assessment of a virtual patient

Abstract

Purpose

Existing research suggests that while some laboratories report variants of uncertain significance, unsolicited findings (UF), and/or secondary findings (SF) when performing exome sequencing, others do not.

Methods

To investigate reporting differences, we created virtual patient–parent trio data by merging variants from patients into “normal” exomes. We invited laboratories worldwide to analyze the data along with patient phenotype information (developmental delay, dysmorphic features, and cardiac hypertrophy). Laboratories issued a diagnostic exome report and completed questionnaires to explain their rationale for reporting (or not reporting) each of the eight variants integrated.

Results

Of the 39 laboratories that completed the questionnaire, 30 reported the HDAC8 variant, which was a partial cause of the patient’s primary phenotype, and 26 reported the BICD2 variant, which explained another phenotypic component. Lack of reporting was often due to using a filter or a targeted gene panel that excluded the variant, or because they did not consider the variant to be responsible for the phenotype. There was considerable variation in reporting variants associated with the cardiac phenotype (MYBPC3 and PLN) and reporting UF/SF also varied widely.

Conclusion

This high degree of variability has significant impact on whether causative variants are identified, with important implications for patient care.

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Acknowledgements

D.F.V. is a Postdoctoral Research Fellow of the Research Foundation–Flanders (FWO Vlaanderen) and also acknowledges the infrastructure funding received from the Victorian State Government through the Operational Infrastructure Support (OIS) Program.

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Correspondence to Danya F. Vears PhD.

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Vears, D.F., Elferink, M., Kriek, M. et al. Analysis of laboratory reporting practices using a quality assessment of a virtual patient. Genet Med (2020). https://doi.org/10.1038/s41436-020-01015-7

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Keywords

  • next-generation sequencing
  • genomic sequencing
  • exome sequencing
  • quality assurance
  • bioethics

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