Curating the Clinical Genome 2024 ePoster Gallery-Reanalysis of Pediatric Cohort Undergoing Hereditary Cancer Predisposition Testing Using Bayesian Classification Framework

Reanalysis of Pediatric Cohort Undergoing Hereditary Cancer Predisposition Testing Using Bayesian Classification Framework

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The study compared the variant classifications in 115 hereditary cancer predisposition genes using the ACMG/AMP 2015 guidelines and a Bayesian point-based system in 721 pediatric patients. The point system reduced the rate of variants of unknown significance (VUS) to 15% compared to 36% by the ACMG/AMP 2015 guidelines. This reduction was achieved by downgrading VUS based on single benign supporting evidence, single benign strong evidence, and resolving conflicting evidence. Approximately 8% of variants classified by the point system aligned with the reported classifications, leading to the upgrading of one VUS to likely pathogenic. The point system offers a systematic approach for the reanalysis of VUS in hereditary cancer genes, facilitating a decrease in VUS rate and providing a structured method for periodic reevaluation. The study highlights the utility of the Bayesian point-based system in improving variant classification accuracy and guiding clinical decision-making in hereditary cancer predisposition testing.

Keywords

variant classifications

hereditary cancer predisposition genes

ACMG/AMP 2015 guidelines

Bayesian point-based system

pediatric patients

variants of unknown significance

VUS rate

systematic approach

reanalysis of VUS

clinical decision-making

Mohammad Eldomery (mohammad.eldomery@stjude.org)