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.
- Telegenetics, a form of telemedicine, is 2-way, interactive real-time electronic information communication between a patient and genetics health care professional(s) (ie, medical geneticists [physicians who specialize in genetics] and genetic counselors [health care workers with training in medical genetics and counseling]) as an alternate to providing health care in person at a medical office.1,2 These services include, but are not limited to, assessment, diagnosis, consultation, test result release, education, counseling, management of care, and/or aided self-management.
- The American College of Medical Genetics and Genomics (ACMG) previously published guidance for reporting secondary findings (SF) in the context of clinical exome and genome sequencing in 2013, 2017, and 2021.1-3 The ACMG Secondary Findings Working Group (SFWG) and Board of Directors (BOD) have agreed that the list of recommended genes should now be updated annually, but with an ongoing goal of maintaining this as a minimum list. Reporting of SF should be considered neither a replacement for indication-based diagnostic clinical genetic testing nor a form of population screening.
- Noninvasive prenatal screening (NIPS) using cell-free DNA has been assimilated into prenatal care. Prior studies examined clinical validity and technical performance in high-risk populations. This systematic evidence review evaluates NIPS performance in a general-risk population.
- Hearing loss is a common and complex condition that can occur at any age, can be inherited or acquired, and is associated with a remarkably wide array of etiologies. The diverse causes of hearing loss, combined with the highly variable and often overlapping presentations of different forms of hearing loss, challenge the ability of traditional clinical evaluations to arrive at an etiologic diagnosis for many deaf and hard-of-hearing individuals. However, identifying the etiology of hearing loss may affect clinical management, improve prognostic accuracy, and refine genetic counseling and assessment of the likelihood of recurrence for relatives of deaf and hard-of-hearing individuals.
- We thank Righetti et al1 for their interest in our article titled Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG).2 We were pleased to learn that the investigators from the Australian Reproductive Genetic Carrier Screening Project (ARGCSP) are in agreement with many aspects of this practice resource.
- Pharmacogenomic testing interrogates germline sequence variants implicated in interindividual drug response variability to infer a drug response phenotype and to guide medication management for certain drugs. Specifically, discrete aspects of pharmacokinetics, such as drug metabolism, and pharmacodynamics, as well as drug sensitivity, can be predicted by genes that code for proteins involved in these pathways. Pharmacogenomics is unique and differs from inherited disease genetics because the drug response phenotype can be drug-dependent and is often unrecognized until an unexpected drug reaction occurs or a patient fails to respond to a medication.
- Assays that measure lysosomal enzyme activity are important tools for the screening and diagnosis of lysosomal storage disorders (LSDs). They are often ordered in combination with urine oligosaccharide and glycosaminoglycan analysis, additional biomarker assays, and/or DNA sequencing when an LSD is suspected. Enzyme testing in whole blood/leukocytes, serum/plasma, cultured fibroblasts, or dried blood spots demonstrating deficient enzyme activity remains a key component of LSD diagnosis and is often prompted by characteristic clinical findings, abnormal newborn screening, abnormal biochemical findings (eg, elevated glycosaminoglycans), or molecular results indicating pathogenic variants or variants of uncertain significance in a gene associated with an LSD.
- Human genomic data linked to health records have become valuable in the quest to establish correlations between disease and genetic information. As a result, it has become increasingly common for patient genetic information obtained through clinical testing or other means to be de-identified and linked to health records for sale or transfer to a third party for research and development purposes (eg, novel drug targets, patient and provider tools for managing health care). Unlike many other elements within the de-identified data set, however, the patient’s genetic information in various forms (eg, DNA sequence, RNA sequence, aggregated variant data, optical mapping) may be sufficiently information-rich to permit reidentification of the patient using informatics tools in some cases and is considered by some to be inherently identifiable.
- In this era of precision medicine, the incorporation of genetic and genomic information, herein referred to as genetic information, into health care has gained unprecedented attention. As a result of the rapid decline in the cost of DNA sequencing, these data are now routinely used for diagnostic purposes and preventive health screening. In addition to the application of genetic information to support diagnosis and management, consumers may directly access various genetic testing–based products for medical and nonmedical uses, and some employers now offer wellness genetic testing to their employees as a benefit.
- Genomic testing, including single-nucleotide variation (formerly single-nucleotide polymorphism)–based chromosomal microarray and exome and genome sequencing, can detect long regions of homozygosity (ROH) within the genome. Genomic testing can also detect possible uniparental disomy (UPD). Platforms that can detect ROH and possible UPD have matured since the initial American College of Medical Genetics and Genomics (ACMG) standard was published in 2013, and the detection of ROH and UPD by these platforms has shown utility in diagnosis of patients with genetic/genomic disorders.
- This document was retired by the American College of Medical Genetics and Genomics (ACMG) Board of Directors as of May 20, 2019 with the following addendum.