2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Integration of RNA Sequencing Improves Hereditary Cancer Genetic Testing

Pdf Summary

This study aimed to investigate the impact of RNA sequencing on the detection and reclassification of variants of uncertain significance (VUSs) related to splicing in hereditary cancer genetic testing. The researchers conducted a retrospective analysis of data from individuals who received the test between October 2021 and October 2022. Variants predicted to impact splicing were further analyzed using RNA sequencing. Among 236 initially classified VUSs, RNA sequencing resolved 22% (52/236) of them. This resulted in 7.2% (17/236) being upgraded to likely pathogenic and 14.8% (35/236) being downgraded into not reportable. The majority of VUSs (78%, 184/236) remained unchanged. Missense variants were the most frequently upgraded, followed by intronic variants and synonymous variants. Additionally, 50% of synonymous variants and 16.5% of intronic variants were downgraded, while no missense variants were downgraded. Among the variants upgraded to likely pathogenic, the majority were identified as clinically actionable genes. The study highlights that RNA sequencing can improve the interpretation of VUSs related to splicing, with potential implications for cancer risk assessment, management, and treatment.

Asset Subtitle

Presenting Author - Youbao Sha, PhD, FACMG; Co-Author - J. Bryce Ortiz, PhD; Co-Author - Kate Loranger, MS, CGC; Co-Author - Bryne Ulmschneider, PhD; Co-Author - Jeffrey N. Weitzel, MD; Co-Author - Wenbo Xu, MD, PhD, FACMG;

Meta Tag

Variant Detection

Sequencing

NextGen Sequencing

Genetic Testing

Cell free DNA/cfDNA

Cancer Syndromes

Co-Author Wenbo Xu, MD, PhD, FACMG

Co-Author Jeffrey N. Weitzel, MD

Co-Author Bryne Ulmschneider, PhD

Co-Author Kate Loranger, MS, CGC

Co-Author J. Bryce Ortiz, PhD

Presenting Author Youbao Sha, PhD, FACMG

Keywords

RNA sequencing

variants of uncertain significance

splicing

hereditary cancer genetic testing

retrospective analysis

likely pathogenic

not reportable

missense variants

intronic variants

synonymous variants