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2023 ACMG Annual Clinical Genetics Meeting Digital ...
Integration of RNA Sequencing Improves Hereditary ...
Integration of RNA Sequencing Improves Hereditary Cancer Genetic Testing
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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
Cancer Syndromes
Cell free DNA/cfDNA
Genetic Testing
NextGen Sequencing
Sequencing
Variant Detection
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
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
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