“We observed up to 11.5% of genetic disorders with inflation in pathogenic variant sets and up to 92.3% for the variant set with conflicting interpretations. This improved to 7.7% and 57.7%, respectively, after filtering for disease-specific allele frequency. The patterns of inflation were replicated using public data from more than 138,000 genomes. The burden of rare variants was a main contributing factor of the observed inflation, indicating collective misclassified rare variants. We also analyzed the dynamics of re-classification of variant pathogenicity in ClinVar over time, which indicates progressive improvement in variant classification. The study shows that databases include a significant proportion of wrongly ascertained variants; however, it underscores the critical role of ClinVar to contrast claims and foster validation across submitters.”
Recent Posts
- April/May 2023 – The Data Driven Point of View
- Bryan Warf, PhD Joins The Center for Genomic Interpretation Team as Senior Director of Scientific Affairs
- The Center for Genomic Interpretation Launches ELEVATEGENETICS VERIFY
- March 2023 – The Data Driven Point of View
- Center For Genomic Interpretation Seeks Nominations of ELEVATEGENETICS Acceptable Thresholds Committee
Recent Comments