Dataset Information

Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).

ABSTRACT: PURPOSE:Copy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital anomalies, as well as for fetuses with ultrasound abnormalities. In the decade that this analysis has been in widespread clinical use, tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population. However, continued broad implementation of array and next-generation sequencing-based technologies will expand the types of CNVs encountered in the clinical setting, as well as our understanding of their impact on human health. METHODS:To assist clinical laboratories in the classification and reporting of CNVs, irrespective of the technology used to identify them, the American College of Medical Genetics and Genomics has developed the following professional standards in collaboration with the National Institutes of Health (NIH)-funded Clinical Genome Resource (ClinGen) project. RESULTS:This update introduces a quantitative, evidence-based scoring framework; encourages the implementation of the five-tier classification system widely used in sequence variant classification; and recommends "uncoupling" the evidence-based classification of a variant from its potential implications for a particular individual. CONCLUSION:These professional standards will guide the evaluation of constitutional CNVs and encourage consistency and transparency across clinical laboratories.

SUBMITTER: Riggs ER

PROVIDER: S-EPMC7313390 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).

Riggs Erin Rooney ER Andersen Erica F EF Cherry Athena M AM Kantarci Sibel S Kearney Hutton H Patel Ankita A Raca Gordana G Ritter Deborah I DI South Sarah T ST Thorland Erik C EC Pineda-Alvarez Daniel D Aradhya Swaroop S Martin Christa Lese CL

Genetics in medicine : official journal of the American College of Medical Genetics 20191106 2

<h4>Purpose</h4>Copy-number analysis to detect disease-causing losses and gains across the genome is recommended for the evaluation of individuals with neurodevelopmental disorders and/or multiple congenital anomalies, as well as for fetuses with ultrasound abnormalities. In the decade that this analysis has been in widespread clinical use, tremendous strides have been made in understanding the effects of copy-number variants (CNVs) in both affected individuals and the general population. Howeve ...[more]

PMID: 31690835

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Project description:The American College of Medical Genetics and Genomics (ACMG) previously developed guidance for the interpretation of sequence variants.(1) In the past decade, sequencing technology has evolved rapidly with the advent of high-throughput next-generation sequencing. By adopting and leveraging next-generation sequencing, clinical laboratories are now performing an ever-increasing catalogue of genetic testing spanning genotyping, single genes, gene panels, exomes, genomes, transcriptomes, and epigenetic assays for genetic disorders. By virtue of increased complexity, this shift in genetic testing has been accompanied by new challenges in sequence interpretation. In this context the ACMG convened a workgroup in 2013 comprising representatives from the ACMG, the Association for Molecular Pathology (AMP), and the College of American Pathologists to revisit and revise the standards and guidelines for the interpretation of sequence variants. The group consisted of clinical laboratory directors and clinicians. This report represents expert opinion of the workgroup with input from ACMG, AMP, and College of American Pathologists stakeholders. These recommendations primarily apply to the breadth of genetic tests used in clinical laboratories, including genotyping, single genes, panels, exomes, and genomes. This report recommends the use of specific standard terminology-"pathogenic," "likely pathogenic," "uncertain significance," "likely benign," and "benign"-to describe variants identified in genes that cause Mendelian disorders. Moreover, this recommendation describes a process for classifying variants into these five categories based on criteria using typical types of variant evidence (e.g., population data, computational data, functional data, segregation data). Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends that clinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments-approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.

Project description:BackgroundReporting guidelines for different study designs are currently available to report studies with accuracy and transparency. There is a need to develop supplementary guideline items that are specific to areas within Pediatric Dentistry. This study aims to develop Reporting stAndards for research in PedIatric Dentistry (RAPID) guidelines using a pre-defined expert consensus-based Delphi process.MethodsThe development of the RAPID guidelines was based on the Guidance for Developers of Health Research Reporting Guidelines. Following a comprehensive search of the literature, the Executive Group identified ten themes in Pediatric Dentistry and compiled a draft checklist of items under each theme. The themes were categorized as: General, Oral Medicine, Pathology and Radiology, Children with Special Health Care Needs, Sedation and Hospital Dentistry, Behavior Guidance, Dental Caries, Preventive and Restorative Dentistry, Pulp Therapy, Traumatology, and Interceptive Orthodontics. A RAPID Delphi Group (RDG) was formed comprising of 69 members from 15 countries across six continents. Items were scored using a 9-point rating Likert scale. Items achieving a score of seven and above, marked by at least 70% of RDG members were accepted into the RAPID checklist items. Weighted mean scores were calculated for each item. Statistical significance was set at p < 0.05 and one-way ANOVA was used to calculate the difference in the weighted mean scores between the themes.ResultsThe final RAPID checklist comprised of 128 items that were finalized and approved by the RDG members in the online consensus meeting. The percentage for high scores (scores 7 to 9) ranged from 69.57 to 100% for individual items. The overall weighted mean score of the final items ranged from 7.51 to 8.28 (out of 9) and the difference was statistically significant between the themes (p < 0.05).ConclusionsThe RAPID statement provides guidance to researchers, authors, reviewers and editors, to ensure that all elements relevant to particular studies are adequately reported.

Dataset Information

Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).

Publications

Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).

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