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.
Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)
Of all cancers that develop in women in the United States, breast cancer has the highest incidence, regardless of race or ethnicity, with an estimated 271,270 new cases and 42,260 deaths during 2019.1 Approximately 5–10% of breast cancers are estimated to result from hereditary causes, the majority of which are attributed to pathogenic or likely pathogenic (P/LP) variants in the BRCA1 and BRCA2 (BRCA1/2) genes, although other variants in genes such as PALB2, TP53, PTEN, CDH1, CHEK2, and ATM contribute.Diagnostic gene sequencing panels: from design to report—a technical standard of the American College of Medical Genetics and Genomics (ACMG)
Gene sequencing panels are a powerful diagnostic tool for many clinical presentations associated with genetic disorders. Advances in DNA sequencing technology have made gene panels more economical, flexible, and efficient. Because the genes included on gene panels vary widely between laboratories in gene content (e.g., number, reason for inclusion, evidence level for gene–disease association) and technical completeness (e.g., depth of coverage), standards that address technical and clinical aspects of gene panels are needed.Yield of additional genetic testing after chromosomal microarray for diagnosis of neurodevelopmental disability and congenital anomalies: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
Chromosomal microarray (CMA) is recommended as the first-tier test in evaluation of individuals with neurodevelopmental disability and congenital anomalies. CMA may not detect balanced cytogenomic abnormalities or uniparental disomy (UPD), and deletion/duplications and regions of homozygosity may require additional testing to clarify the mechanism and inform accurate counseling. We conducted an evidence review to synthesize data regarding the benefit of additional testing after CMA to inform a genetic diagnosis.Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics
Disclaimer: These recommendations are designed primarily as an educational resource for medical geneticists and other healthcare providers to help them provide quality medical services. Adherence to these recommendations is completely voluntary and does not necessarily assure a successful medical outcome. These recommendations should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed toward obtaining the same results.Direct-to-consumer genetic testing: a revised position statement of the American College of Medical Genetics and Genomics
Disclaimer: These recommendations are designed primarily as an educational resource for medical geneticists and other health-care providers to help them provide quality medical genetics services. Adherence to these recommendations does not necessarily assure a successful medical outcome. These recommendations 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. In determining the propriety of any specific procedure or test, geneticists and other clinicians should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen.American College of Medical Genetics and Genomics guideline for the clinical evaluation and etiologic diagnosis of hearing loss
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 a 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.Technical report: ethical and policy issues in genetic testing and screening of children
The genetic testing and genetic screening of children are commonplace. Decisions about whether to offer genetic testing and screening should be driven by the best interest of the child. The growing literature on the psychosocial and clinical effects of such testing and screening can help inform best practices. This technical report provides ethical justification and empirical data in support of the proposed policy recommendations regarding such practices in a myriad of settings.Genet Med 2013:15(3):234–245Technical standards and guidelines for spinal muscular atrophy testing
Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron (SMN1) gene, affecting approximately 1 in 10,000 live births. The disease is characterized by progressive symmetrical muscle weakness resulting from the degeneration and loss of anterior horn cells in the spinal cord and brainstem nuclei. The disease is classified on the basis of age of onset and clinical course. Two almost identical SMN genes are present on 5q13: the SMN1 gene, which is the spinal muscular atrophy-determining gene, and the SMN2 gene.Genetic counseling and testing for Alzheimer disease: Joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors
Alzheimer disease is the most common cause of dementia. It occurs worldwide and affects all ethnic groups. The incidence of Alzheimer disease is increasing due, in part, to increased life expectancy and the aging baby boomer generation. The average lifetime risk of developing Alzheimer disease is 10–12%. This risk at least doubles with the presence of a first-degree relative with the disorder. Despite its limited utility, patients express concern over their risk and, in some instances, request testing.Technical standards and guidelines for myotonic dystrophy type 1 testing
Myotonic dystrophy type 1 is an autosomal dominant multisystem condition. Myotonic dystrophy type 1 is the result of an unstable CTG expansion in the 3′-untranslated region of the myotonic dystrophy protein kinase gene. The age of onset and the severity of the phenotype are roughly correlated with the size of the CTG expansion. The combination of Southern transfer and polymerase chain reaction provides an accurate means of identifying patients affected by myotonic dystrophy type 1. This document follows the outline format of the general Standards and Guidelines for Clinical Genetics Laboratories.Carrier screening for spinal muscular atrophy
The autosomal recessive disorder proximal spinal muscular atrophy (SMA, MIM #253300) is a severe neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, which results in progressive proximal muscle weakness and paralysis. SMA is the second most common fatal autosomal recessive disorder after cystic fibrosis, with an estimated prevalence of 1 in 10,000 live births and a carrier frequency of 1/40–1/60. Childhood SMA is subdivided into three clinical groups on the basis of age of onset and clinical course: type I SMA (Werdnig-Hoffmann) is characterized by severe, generalized muscle weakness and hypotonia at birth or within the first 3 months.Carrier screening in individuals of Ashkenazi Jewish descent
This guideline is designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to this guideline does not necessarily assure a successful medical outcome. This guideline 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. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen.Preconception and prenatal testing of biologic fathers for carrier status
Disclaimer: This guideline is designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to this guideline does not necessarily assure a successful medical outcome. This guideline 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. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen.Fragile X syndrome: Diagnostic and carrier testing
Disclaimer: This guideline is designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services. Adherence to this guideline does not necessarily assure a successful medical outcome. This guideline 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. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen.Standards and Guidelines for CFTR Mutation Testing
One mission of the ACMG Laboratory Quality Assurance (QA) Committee is to develop standards and guidelines for clinical genetics laboratories, including cytogenetics, biochemical, and molecular genetics specialties. This document was developed under the auspices of the Molecular Subcommittee of the Laboratory QA Committee by the Cystic Fibrosis (CF) Working Group. It was placed on the “fast track” to address the preanalytical, analytical, and postanalytical quality assurance practices of laboratories currently providing testing for CF.Genetics Evaluation Guidelines for the Etiologic Diagnosis of Congenital Hearing Loss
The advent of hearing screening in newborns in many states has led to an increase in the use of genetic testing and related genetic services in the follow-up of infants with hearing loss. A significant proportion of those with congenital hearing loss have genetic etiologies underlying their hearing loss. To ensure that those identified with congenital hearing loss receive the genetic services appropriate to their conditions, the Maternal and Child Health Bureau of the Health Resources and Services Administration funded the American College of Medical Genetics to convene an expert panel to develop guidelines for the genetic evaluation of congential hearing loss.
