2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Clinical Utility of all Types of Medically Relevant Secondary findings: A Systematic Evidence Review

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This document provides an overview of a systematic review on the clinical utility of secondary findings in genomic sequencing. The study aimed to review and synthesize evidence on all types of medically relevant secondary findings. The researchers analyzed a total of 88 studies that included a variety of populations undergoing sequencing, including adults, pediatric, and fetal samples, as well as healthy populations. The primary outcomes of interest were the frequency of secondary findings, the impact of secondary findings on clinical management, and the concordance between secondary findings and patient phenotype or family history.<br /><br />The preliminary results showed that 58% of studies used the ACMG-AMP criteria for variant interpretation. The frequency of secondary findings varied across studies, ranging from 0.25% to 100% of participants. The number of genes analyzed as secondary findings ranged from 3 to over 3000. Medically actionable variants were found in 0.25% to 8% of participants, non-actionable variants in 0.71% to 12%, carrier status for recessive conditions in 4% to 94%, and pharmacogenomic variants in 64% to 100%.<br /><br />Regarding the impact on clinical management, some studies indicated that secondary findings had utility in explaining undiagnosed personal or family history of disease. However, clinical outcomes of disclosing secondary findings were not well-addressed. Only a few studies reported medical actions taken based on secondary findings, with varying proportions of patients completing each action.<br /><br />Concordance between secondary findings and phenotype or family history was also assessed. Some studies found that no participants had clinical manifestations consistent with their secondary findings, while others found a proportion of participants with relevant clinical features or a clinical diagnosis. Similarly, some studies found no participants with a family history consistent with the associated condition, while others found a proportion with a consistent family history.<br /><br />Overall, the document highlights the need for rigorous evidence synthesis and critical appraisal to guide the practice and policy of secondary finding disclosure in genomic sequencing. Future studies should focus on collecting clinical data following results disclosure and examining the clinical outcomes of secondary findings.

Asset Subtitle

Presenting Author - Chloe Mighton, MSc; Co-Author - Vaness Rokoszak, MHSc; Co-Author - Simran Dhaliwal, BSc; Co-Author - Safa Majeed, MSc; Co-Author - Vernie Aguda, MSc; Co-Author - Sonya Grewal, HBSc; Co-Author - Agnes Sebastian, MSc; Co-Author - Salma Shickh, MS, CGC; Co-Author - David Lightfoot, PhD; Co-Author - Yvonne Bombard, PhD;

Meta Tag

Exome sequencing

Genetic Testing

Genome sequencing

Policy Issues

Sequencing

Co-Author Vaness Rokoszak, MHSc

Co-Author Simran Dhaliwal, BSc

Co-Author Safa Majeed, MSc

Co-Author Vernie Aguda, MSc

Co-Author Sonya Grewal, HBSc

Co-Author Agnes Sebastian, MSc

Co-Author Salma Shickh, MS, CGC

Co-Author David Lightfoot, PhD

Co-Author Yvonne Bombard, PhD

Presenting Author Chloe Mighton, MSc

Keywords

systematic review

clinical utility

secondary findings

genomic sequencing

medically relevant

frequency

clinical management

concordance

ACMG-AMP criteria

variant interpretation