Points to consider for laboratories reporting results from diagnostic genomic sequencing

Area of Science:

• Clinical Genetics
• Molecular Diagnostics
• Bioinformatics

Background:

• Next-generation sequencing (NGS) is crucial for diagnosing genetic diseases.
• Current professional guidelines offer inconsistent recommendations on reporting specific types of genetic findings.

Purpose of the Study:

• To address inconsistencies in reporting guidelines for diagnostic NGS.
• To develop practical points to consider for laboratories reporting NGS results.

Main Methods:

• Review of existing professional guidelines for NGS reporting.
• Incorporation of interdisciplinary working group experiences.
• Consideration of data from a qualitative study on NGS reporting.

Main Results:

• Identified inconsistencies in guidance on reporting variants of uncertain significance (VUS), unsolicited findings (UF), and secondary findings (SF).
• Highlighted differing approaches to data reanalysis and re-contact.
• Developed a framework of points to consider across six key categories for diagnostic NGS reporting.

Conclusions:

• The developed points to consider aim to assist diagnostic laboratories in standardizing reporting processes.
• Addressing VUS and UF reporting is critical for effective clinical implementation of NGS.
• Further refinement of reporting practices is needed to optimize the utility of diagnostic NGS.