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Dutch genome diagnostic laboratories accelerated and improved variant interpretation and increased accuracy by sharing data
- Source :
- Human Mutation, 40, 2230-2238, Fokkema, I F A C, van der Velde, K J, Slofstra, M K, Ruivenkamp, C A L, Vogel, M J, Pfundt, R, Blok, M J, Lekanne Deprez, R H, Waisfisz, Q, Abbott, K M, Sinke, R J, Rahman, R, Nijman, I J, de Koning, B, Thijs, G, Wieskamp, N, Moritz, R J G, Charbon, B, Saris, J J, den Dunnen, J T, Laros, J F J, Swertz, M A & van Gijn, M E 2019, ' Dutch genome diagnostic laboratories accelerated and improved variant interpretation and increased accuracy by sharing data ', Human Mutation, vol. 40, no. 12, pp. 2230-2238 . https://doi.org/10.1002/humu.23896, Human Mutation, 40(12), 2230-2238. Wiley, Human Mutation, Human Mutation, 40(12), 2230-2238. Wiley-Liss Inc., Human mutation, 40(12), 2230-2238. Wiley-Liss Inc., Human Mutation, 40(12), 2230. Wiley-Liss Inc., Human Mutation, 40(12), 2230-2238. WILEY, Human Mutation, 40, 12, pp. 2230-2238
- Publication Year :
- 2019
-
Abstract
- Each year diagnostic laboratories in the Netherlands profile thousands of individuals for heritable disease using next‐generation sequencing (NGS). This requires pathogenicity classification of millions of DNA variants on the standard 5‐tier scale. To reduce time spent on data interpretation and increase data quality and reliability, the nine Dutch labs decided to publicly share their classifications. Variant classifications of nearly 100,000 unique variants were catalogued and compared in a centralized MOLGENIS database. Variants classified by more than one center were labeled as “consensus” when classifications agreed, and shared internationally with LOVD and ClinVar. When classifications opposed (LB/B vs. LP/P), they were labeled “conflicting”, while other nonconsensus observations were labeled “no consensus”. We assessed our classifications using the InterVar software to compare to ACMG 2015 guidelines, showing 99.7% overall consistency with only 0.3% discrepancies. Differences in classifications between Dutch labs or between Dutch labs and ACMG were mainly present in genes with low penetrance or for late onset disorders and highlight limitations of the current 5‐tier classification system. The data sharing boosted the quality of DNA diagnostics in Dutch labs, an initiative we hope will be followed internationally. Recently, a positive match with a case from outside our consortium resulted in a more definite disease diagnosis.
- Subjects :
- data sharing
Guidelines as Topic
Biology
Dna variants
computer.software_genre
Genome
RECOMMENDATIONS
CLASSIFICATION
03 medical and health sciences
Databases
All institutes and research themes of the Radboud University Medical Center
Databases, Genetic
Genetics
SEQUENCE VARIANTS
diagnostics
Humans
Genetics(clinical)
whole-exome sequencing
Genetics (clinical)
Exome sequencing
database
030304 developmental biology
Netherlands
0303 health sciences
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
business.industry
Information Dissemination
CARDIOMYOPATHIES
030305 genetics & heredity
Genetic Diseases, Inborn
Data interpretation
Genetic Variation
High-Throughput Nucleotide Sequencing
Sequence Analysis, DNA
Pathogenicity
Penetrance
3. Good health
Data Accuracy
Data sharing
Data quality
NGS
whole‐exome sequencing
Artificial intelligence
business
Laboratories
computer
Natural language processing
Subjects
Details
- ISSN :
- 10597794
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- Human Mutation
- Accession number :
- edsair.doi.dedup.....12ed75f037a58c36a8d55cf91aaaa300