ACMG Statements and Guidelines
These online statements and guidelines are definitive and may be cited using the digital object identifier (DOI). These recommendations are designed primarily as an educational resource for medical geneticists and other healthcare providers to help them provide quality medical genetics services; they should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. Please refer to the leading disclaimer in each document for more information.
Incidental detection of acquired variants in germline genetic and genomic testing: a points to consider statement of the American College of Medical Genetics and Genomics (ACMG)
With recent advances in DNA sequencing technology, it is now possible to begin to appreciate the full scope of DNA variation that arises over the course of an individual’s lifetime.1,2 Our understanding of how the human genome changes over time and in response to external exposures is growing with the improved availability of next-generation sequencing (NGS) based testing, including exome/genome sequencing of large patient cohorts. Clinical laboratories employing NGS-based methodologies can detect many types of DNA sequence variation including those that are present at a reduced variant allele fraction (VAF) (i.e., less than the 50% expected for a heterozygous germline finding).Points to consider when assessing relationships (or suspecting misattributed relationships) during family-based clinical genomic testing: a statement of the American College of Medical Genetics and Genomics (ACMG)
Trio-based genetic analysis (typically involving a child and their biological parents) is an important tool in clinical diagnostic testing, as this type of analysis aids in developing an accurate understanding of the inheritance of variants observed in the proband.1-5 Understanding if a variant is inherited or is de novo can directly affect variant classification and result interpretation; consequently, misunderstanding the true biological relationship between analyzed samples can lead to erroneous clinical interpretations.CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG)
Pathogenic variants in the CFTR gene are causative of classic cystic fibrosis (CF) as well as some nonclassic CF phenotypes. In 2001, CF became the first target of pan-ethnic universal carrier screening by molecular methods. The American College of Medical Genetics and Genomics (ACMG) recommended a core panel of 23 disease-causing variants as the minimal set to be included in pan-ethnic carrier screening of individuals with no family history of the disease, and these variants were usually assessed using targeted methods.Points to consider in the reevaluation and reanalysis of genomic test results: a statement of the American College of Medical Genetics and Genomics (ACMG)
Reductions in the cost of genomic analyses and the elimination of gene patents for clinical diagnostics have enabled clinical laboratories to provide increasingly comprehensive genetic testing using sequencing, microarrays, and other methods, resulting in the generation of a vast amount of data that then needs to be analyzed.1 A significant challenge for clinical laboratory geneticists is the provision of accurate and consistent variant classification. Variant classification has historically been hindered by a lagging recognition of gene–disease associations, as well as a lack of publicly available data (including reference data) from clinical laboratories and other sources.Patient re-contact after revision of genomic test results: points to consider—a statement of the American College of Medical Genetics and Genomics (ACMG)
Nearly two decades ago, the American College of Medical Genetics (now the American College of Medical Genetics and Genomics [ACMG]) Policy Statement “Duty to re-contact” was prescient in highlighting the increasingly important issue of patient re-contact.1 Originally focused on clinical genetics practice, its importance now extends to both medical genomics and medical practice in general. Next-generation genomic testing, including multigene panels, exome sequencing (ES), and genome sequencing (GS), is permitting ever larger amounts of data to be collected on each patient sample, with a corresponding increase in the complexity of the results.ACMG clinical laboratory standards for next-generation sequencing
Next-generation sequencing technologies have been and continue to be deployed in clinical laboratories, enabling rapid transformations in genomic medicine. These technologies have reduced the cost of large-scale sequencing by several orders of magnitude, and continuous advances are being made. It is now feasible to analyze an individual’s near-complete exome or genome to assist in the diagnosis of a wide array of clinical scenarios. Next-generation sequencing technologies are also facilitating further advances in therapeutic decision making and disease prediction for at-risk patients.
