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.
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.
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.
This high degree of variability has significant impact on whether causative variants are identified, with important implications for patient care.
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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.
The authors declare no conflicts of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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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
- next-generation sequencing
- genomic sequencing
- exome sequencing
- quality assurance
European Journal of Human Genetics (2020)