We are excited to inform you that Geneyx has incorporated the latest guidelines from the American College of Medical Genetics and Genomics (ACMG) regarding secondary findings.
In accordance with the recently published article titled “Secondary Findings from Clinical Genomic Sequencing: Prevalence, Patient Perspectives, Family Impact, and Healthcare Costs” we have updated our platform to include the following genes as recommended secondary findings: CALM1, CALM2, and CALM3.
Whole Exome and Whole Genome Sequencing
The American College of Medical Genetics and Genomics (ACMG) has recently released updated guidelines for reporting secondary findings (SFs) in clinical exome and genome sequencing. The ACMG Secondary Findings Working Group (SFWG) and Board of Directors (BODs) have agreed to update the list of recommended genes annually, with the goal of maintaining it as a minimum list. It is important to note that the reporting of SFs is not a substitute for diagnostic genetic testing or population screening.
The SF list is versioned to differentiate major and minor revisions. Major revisions involve conceptual changes or the addition/removal of a large number of genes, while minor revisions involve the addition/removal of a few genes without policy changes. The current SFWG consists of experts from various disciplines, and they reviewed nomination forms and voted on the inclusion/exclusion of gene-phenotype pairs for the ACMG SF v3.2 list.
The updated SF v3.2 list includes 3 new genes (CALM1, CALM2, and CALM3) associated with long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. The ATP7A gene, associated with Menkes disease, was considered but ultimately excluded from the list. The SFWG’s responsibility is to recommend a minimum list of gene-phenotype pairs for opportunistic screening, aiming to identify/manage risks for genetic disorders through established interventions.
The complete ACMG SF v3.2 list includes genes associated with cancer, cardiovascular conditions, inborn errors of metabolism, and miscellaneous phenotypes. For cancer and inborn errors of metabolism, there were no additions or removals recommended. For cardiovascular conditions, CALM1, CALM2, and CALM3 were recommended for addition to the list. In the miscellaneous phenotypes category, no additions were recommended.
The addition of CALM1, CALM2, and CALM3 to the SF v3.2 list is based on their similar prevalence and penetrance rates to existing genes on the ACMG SF list associated with sudden cardiac death. The exclusion of ATP7A from the list is due to the lack of demonstrated effectiveness and possible toxicity of available treatments for Menkes disease.
It is important to keep in mind that the SF list is not exhaustive and may not cover all possible genetic conditions. The goal is to provide a minimum list for opportunistic screening, and variants classified as pathogenic or likely pathogenic within the included genes should be reported. Variants of uncertain significance should not be reported.
The updated SF v3.2 list aims to enhance the identification and management of genetic disorders through screening, with a focus on established interventions to reduce morbidity and mortality. The list provides valuable guidance for healthcare professionals performing clinical exome and genome sequencing and reinforces the importance of responsible reporting of secondary findings.
