Analysis and Interpretation of Somatic NMD-Escaping Variants in Oncogenes and Dual-Function Genes across Adult and Pediatric Cancer Cohorts.

ABSTRACT: Interpreting protein-truncating variants predicted to escape nonsense-mediated decay (NMDe) based on the 50-bp rule is challenging due to their variable consequences. The Clinical Genome Resource, Cancer Genomics Consortium, and Variant Interpretation for Cancer Consortium recommendations focus on tumor suppressor genes where NMDe variants may result in loss-of-function. However, guidance for interpreting NMDe variants in oncogenes and dual-function genes remains limited. To address this gap, we screened the Catalogue of Somatic Mutations in Cancer, focusing on oncogenes and dual-function genes with ≥10 NMDe variants supported by published functional studies. This analysis prioritized 15 genes exhibiting two distinct NMDe patterns resulting in gene activation. The first pattern and gene ex

SUBMITTER: Eldomery MK 

PROVIDER: S-EPMC12668114 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature