PPM - Laboratory Reporting of Secondary Findings in Clinical Exome and Genome Sequencing-Description and References

Description and References

Pdf Summary

This module provides an overview of the American College of Medical Genetics and Genomics (ACMG) guidelines on reporting secondary findings (SF) from clinical exome sequencing (ES) and genome sequencing (GS). Aimed at clinical laboratory geneticists who perform or interpret ES/GS, it emphasizes important considerations for identifying and reporting SF detected during these analyses. Participants are encouraged to review five recent ES/GS cases from their own labs to apply learning objectives.<br /><br />The ACMG has developed and refined recommendations regarding SF reporting since 2013. Initially, these guidelines focused on clinically actionable SF—genetic variants unrelated to the primary testing indication but potentially significant for patient health. Over time, updates have expanded and clarified the list of genes for which SF should be reported and provided guidance on interpretation and communication to optimize clinical utility and ethical practice.<br /><br />The latest 2025 update, ACMG SF v3.3, presents a carefully curated minimum gene list for reporting SF, prioritizing actionability and patient impact. This update introduces a publicly accessible ClinGen webpage to support clinical laboratories in variant assessment and reporting decisions. The module underscores the dynamic nature of these guidelines, designed to reflect advances in genomics and evolving clinical and ethical considerations.<br /><br />Reviewed literature supporting the module spans the foundational 2013 ACMG recommendations through subsequent updates in 2016, 2021 (versions v3.0 and v3.1), 2023 (v3.2), and the 2025 v3.3 version, providing an evidence-based framework for laboratory practice.<br /><br />In summary, this module equips clinical laboratory geneticists with current, authoritative guidance on implementing ACMG’s evolving standards for SF reporting in ES and GS, thereby enhancing patient care through informed communication of clinically significant genomic findings beyond primary diagnostic targets.

Keywords

American College of Medical Genetics and Genomics

ACMG guidelines

secondary findings

clinical exome sequencing

genome sequencing

clinical laboratory geneticists

ACMG SF v3.3

ClinGen webpage

genomic variant reporting

clinically actionable genetic variants