ACMG Predispositions Report - PromicsEdge WGS
ACMG SF v3.3 Clinical Predisposition Report
The ACMG-Based Predisposition Report identifies pathogenic and likely pathogenic variants across 84 clinically actionable genes using 30x clinical-grade whole genome sequencing (WGS), giving practitioners a structured foundation for targeted screening, specialist referrals, and preventive care conversations with clients.
What Is the ACMG Secondary Findings Framework?
The ACMG Secondary Findings (SF) list is developed and maintained by the American College of Medical Genetics and Genomics. It defines a minimum set of genes where identifying a pathogenic or likely pathogenic variant is considered medically actionable — meaning early detection can change screening protocols, treatment planning, or preventive intervention.
The current ACMG Secondary Findings Working Group includes clinical geneticists, clinical laboratory directors, genetic counselors, cardiologists, a bioethicist, and a pediatrician who also serves as a patient advocate.
Only pathogenic and likely pathogenic variants are returned. Variants of Uncertain Significance (VUS) are not included, per ACMG guidelines.
What the Report Covers
The report screens across 84 genes organized into three clinical categories:
Hereditary Cancer Syndromes
Pathogenic variants linked to breast, ovarian, colorectal, thyroid, and other cancers where early screening and prevention are proven to improve outcomes. Key genes include BRCA1, BRCA2, PALB2, APC, TP53, MLH1, MSH2, MSH6, PMS2, and RET.
Cardiovascular Conditions
Genetic risks tied to cardiomyopathies, arrhythmias, sudden cardiac death, and inherited cholesterol disorders that may require monitoring, medication, or specialist referral. Key genes include MYH7, MYBPC3, LMNA, SCN5A, KCNQ1, KCNH2, RYR2, LDLR, APOB, and PCSK9.
Metabolic and Other Clinically Actionable Disorders
Inherited variants affecting endocrine, hematologic, and metabolic pathways — including familial hypercholesterolemia, iron overload disorders, and other conditions where early management can meaningfully improve outcomes. Key genes include HFE, GLA, TSC1, TSC2, and others.
How Results Are Reported
Results are presented in two sections:
- Summary Table — Lists all ACMG SF v3.3 conditions with detection status (Detected / Not Detected), associated genes, and inheritance model (AD, AR, SD, or XL).
- Condition Detail Pages — Generated only for detected findings. Each page includes: ACMG clinical background, the client's specific variant(s) with SNP ID, genotype, chromosome position, and pathogenicity classification, population frequency data, risk interpretation, inheritance explanation, and recommended screening, surveillance, and management guidelines.
Why This Report Matters Clinically
A client's genome may contain high-impact variants with no current symptoms. This report is designed to surface those findings using a rigorous, internationally recognized framework — so practitioners can act before disease presents.
- Identify high-impact genetic risks — Pathogenic variants with strong clinical evidence across cancer, cardiovascular disease, and metabolic disorders.
- Detect risk before disease — Many ACMG conditions benefit from imaging, labs, and surveillance long before symptoms begin.
- Support precision healthcare conversations — Use findings to guide medical decisions, lifestyle recommendations, and specialist referrals.
Note: This report does not diagnose health conditions. Findings should be reviewed in the context of the client's full clinical picture. Clients with actionable results should be referred to a genetic counselor or relevant specialist.