Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar
Autor: | Tina Pesaran, Heidi L. Rehm, Elizabeth C. Chao, Danielle R. Azzariti, Soma Das, Steven M. Harrison, Jill S. Dolinsky, Lisa M. Vincent, Sherri J. Bale, Amy E. Knight Johnson |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_specialty data sharing Concordance MEDLINE 030105 genetics & heredity Article 03 medical and health sciences Databases Genetic medicine Humans Genetic Testing ACMG-AMP guidelines Genetics (clinical) Clinical Laboratory Techniques Genome Human Information Dissemination Extramural variant interpretation Genetic Variation High-Throughput Nucleotide Sequencing ClinVar Genomics 3. Good health Data sharing 030104 developmental biology Family medicine Medical genetics Clinical Laboratory Information Systems Laboratories Psychology Software |
Zdroj: | Genetics in medicine : official journal of the American College of Medical Genetics |
ISSN: | 1098-3600 |
Popis: | Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolve interpretation differences by analyzing a subset of variants. ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the American College of Medical Genetics and Genomics–Association for Molecular Pathology (ACMG-AMP) guidelines, and then compared interpretations. At least two of the participating laboratories interpreted 6,169 variants in ClinVar, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing; 12.8% (31) of reassessed variants remained discordant owing to differences in the application of the ACMG-AMP guidelines. Participating laboratories increased their overall concordance from 88.3 to 91.7%, indicating that sharing variant interpretations in ClinVar—thereby allowing identification of differences and motivation to resolve those differences—is critical to moving toward more consistent variant interpretations. Genet Med advance online publication 09 March 2017 |
Databáze: | OpenAIRE |
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