Free the Data: One Laboratory's Approach to Knowledge-Based Genomic Variant Classification and Preparation for EMR Integration of Genomic Data

Abstract

Current technology allows clinical laboratories to rapidly translate research discoveries from small patient cohorts into clinical genetic tests; therefore, a potentially large proportion of sequence variants identified in individuals with clinical features of a genetic disorder remain unpublished. Without a mechanism for clinical laboratories to share data, interpretation of sequence variants may be inconsistent. We describe here the two components of Emory Genetics Laboratory's (EGL) in-house developed data management system. The first is a highly curated variant database with a data structure designed to facilitate sharing of information about variants identified at EGL with curated databases. This system also tracks changes in variant classifications, creating a record of previous cases in need of updated reports when a classification is changed. The second component, EmVClass, is a Webbased interface that allows any user to view the inventory of variants classified at EGL. These software tools provide a solution to two pressing issues faced by clinical genetics laboratories: how to manage a large variant inventory with evolving variant classifications that need to be communicated to healthcare providers and how to make that inventory of variants freely available to the community.

Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy

“…The global minor allele (T) frequency of this C/T variant is 0.44 27 compared to 0.29 in this trial’s overall population (n=318) and 0.29 in the ethosuximide cohort. Although other CACNA1H variants have been associated with susceptibility to CAE, this variant is considered benign and not disease causing 28 . The variant was mentioned in one study as occurring in both CAE patients and controls 29 indicating this variant is unlikely to contribute to the risk of CAE.…”

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients

“…We analyzed targeted NGS variant data, and identified variants classified according to board standards and guidelines27, 28 (http://www.egl-eurofins.com/emvclass/emvclass.php). Alignment to the human reference genome (hg19) and variant calling was performed using NextGENe ® .…”

“…We analyzed targeted NGS variant data carefully considering other important parameters such as available clinical phenotype information, family history and sequence result (if available) and previous undiagnosed diagnostic genetic test results. Identified variants were classified according to standards and guidelines of the American College of Medical Genetics and Genomics and classification were made available27, 28 (http://www.egl-eurofins.com/emvclass/emvclass.php). Diagnostic yield was calculated based on definitive diagnosis of patients harboring pathogenic variants in autosome‐recessive, ‐dominant, and X‐linked genes and patients with one pathogenic and one variant of uncertain significance (VUS) in the same LGMD gene.…”

Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing

“…Basic information about all variants discussed in this study, including current classification, is available publically online through EmVClass. 18 The design of this study was reviewed and approved by Emory University's Institutional Review Board.…”