2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Evaluation of the ClinGen/CGC/VICC Oncogenicity Guidelines to support Pediatric Variant Classification Workflows

Evaluation of the ClinGen/CGC/VICC Oncogenicity Guidelines to support Pediatric Variant Classification Workflows

Pdf Summary

This document presents an evaluation of the ClinGen/CGC/VICC Oncogenicity Guidelines for pediatric variant classification workflows. The study aimed to integrate these guidelines into a clinical classification workflow. The internal work group reviewed and discussed the guidelines and established a framework and software solution for applying them. However, the study identified challenges in finding resources that provide data from well-established functional studies, supporting variant location in critical domains, and providing pediatric data for automated classification.<br /><br />The study also found it challenging to assess criteria for genes with a single genetic etiology and noted the ambiguity in classifying variants of uncertain significance between the VICC and AMP/ASCO/CAP guidelines, which could lead to confusion and diagnostic errors. Overall, progress has been made in building a framework and process for oncogenicity classification using the guidelines, but there are still questions about how these guidelines will influence clinical reporting and interpretation.<br /><br />The document includes visuals illustrating the process of somatic variant classification and interpretation, the challenges faced in the classification process, and the VarCat interface designed to present data required for the oncogenicity guidelines. It also discusses the importance of well-established in vitro or in vivo functional studies and provides a framework for capturing data on what qualifies as such studies.<br /><br />The study emphasizes the need for evidence-driven refinement of the guidelines and invites feedback on the implementation of the guidelines using a QR code provided.

Asset Subtitle

Presenting Author - Wesley Goar, PhD; Co-Author - Kori Kuzma, B.S.; Co-Author - Kathryn Stahl, B.S.; Co-Author - Kyle Voytovich, B.S.; Co-Author - Mariam T. Mathew, PhD, FACMG; Co-Author - Erica L. Macke, PhD; Co-Author - Melanie Babcock, PhD; Co-Author - Ying-Chen Claire Hou, PhD; Co-Author - Liana G. Hernandez, MS; Co-Author - Jordan R. Olberding, MS; Co-Author - Prasad Kopparapu, PhD; Co-Author - Vijayakumar Jayaraman, MS; Co-Author - Don Corsmeier, MSc; Co-Author - Jessica L. Howard, MB(ASCP); Co-Author - Douglas Depoorter, MS; Co-Author - Ashley Kubatko, MS, PMP; Co-Author - Grant E. Lammi, BS; Co-Author - Marco L. Leung, PhD, FACMG; Co-Author - Kathleen M. Schieffer, PhD; Co-Author - Yassmine Akkari, PhD, FACMG; Co-Author - Elaine R. Mardis, PhD; Co-Author - Peter White, PhD; Co-Author - Catherine E. Cottrell, PhD; Co-Author - Alex H. Wagner, PhD;

Meta Tag

Bioinformatics

Databases

Exome sequencing

Genetic Testing

Genome sequencing

Identification of Disease Genes

Methodology

Molecular Pathophysiology

Oncogenesis

Co-Author Kori Kuzma, B.S.

Co-Author Kathryn Stahl, B.S.

Co-Author Kyle Voytovich, B.S.

Co-Author Mariam T. Mathew, PhD, FACMG

Co-Author Erica L. Macke, PhD

Co-Author Melanie Babcock, PhD

Co-Author Ying-Chen Claire Hou, PhD

Co-Author Liana G. Hernandez, MS

Co-Author Jordan R. Olberding, MS

Co-Author Prasad Kopparapu, PhD

Co-Author Vijayakumar Jayaraman, MS

Co-Author Don Corsmeier, MSc

Co-Author Jessica L. Howard, MB(ASCP)

Co-Author Douglas Depoorter, MS

Co-Author Ashley Kubatko, MS, PMP

Co-Author Grant E. Lammi, BS

Co-Author Marco L. Leung, PhD, FACMG

Co-Author Kathleen M. Schieffer, PhD

Co-Author Yassmine Akkari, PhD, FACMG

Co-Author Elaine R. Mardis, PhD

Co-Author Peter White, PhD

Co-Author Catherine E. Cottrell, PhD

Co-Author Alex H. Wagner, PhD

Presenting Author Wesley Goar, PhD

Keywords

ClinGen/CGC/VICC Oncogenicity Guidelines

pediatric variant classification workflows

clinical classification workflow

framework and software solution

well-established functional studies

variant location in critical domains

pediatric data for automated classification

genes with a single genetic etiology

variants of uncertain significance

oncogenicity classification