Omicia Implements ACMG Variant Scoring and Classification Guidelines to Drive Clinical NGS Report Consistency and Throughput

Omicia Inc. will launch its new ACMG-scoring module for the Opal Clinical™ interpretation and reporting software platform at the ACMG Annual Clinical Genetics Meeting in Tampa, March 8-12th.

This functionality provides an intuitive interface and workflow for clinical testing labs to systematically assess the disease-causing potential of genetic variants using the evidence-based classification system defined in the 2015 Standards and Guidelines for the Interpretation of Sequence Variants.

Published as a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG), the Association for Molecular Pathology (AMP), and the College of American Pathologists (CAP), the guidelines were developed to standardize interpretation and reporting of genomic test results. Through systematic assessment of twenty-eight weighted criteria, variants are ultimately classified on a five-point scale: benign, likely benign, uncertain significance, likely pathogenic and pathogenic.

While recognized as a valuable framework to support consistency of reporting within and between clinical labs, several challenges have arisen for labs attempting to implement the ACMG guidelines for their genomic testing services, including: gathering the myriad pertinent evidence required to address each criterion; developing an efficient, repeatable workflow to assess the criteria; and automating the scoring and classification process for reliable, high-throughput reporting.

Opal Clinical's scoring and classification system solves these challenges, enabling labs to easily adopt the ACMG guidelines and accelerate interpretation with a stepwise, guided assessment of each ACMG criterion. Opal integrates over 90 public and proprietary data sources to bring the specific gene and variant annotations required to make an assessment of the indicated criterion, and provides a simple yes-or-no checkbox evaluation for scoring. As criteria evaluation progresses, Opal calculates an inferred classification that can users can accept or override based on their evaluation of the evidence.

“Applying the ACMG guidelines using Opal Clinical software can improve consistency across interpreters because it represents a logical, systematic way to work through the criteria”, said Jeanette McCarthy, Adjunct Associate Professor at Duke University and the Genomic Medicine Initiative at the University of California-San Francisco in a recent web-based review of her use of the system. “The Opal platform improves efficiency because it brings all the data sources needed for interpretation to the user and the system captures decisions at every step.”

As well as driving consistency, Opal Clinical features several time-saving functions that are essential for labs processing large numbers of clinical tests. A Scoring History database is instantaneously updated as variants are classified within the platform. Variants that have been previously assessed are flagged, and historical classifications, notes and citations can be used for bulk classification and automated reporting. This greatly speeds lab test turnaround times, making clinical testing with targeted sequencing panels, exomes, and whole genomes feasible at high throughput.

Learn more about the Opal Clinical ACMG-scoring module at the ACMG conference in Tampa, March 8-12th : Omicia booth #517 and at a workshop “Software-Enabled Application of the ACMG Guidelines” on Thursday March 10 at 11:40am in Exhibit Theater #2.