Identification and interpretation of TET2 noncanonical splicing site intronic variants in myeloid neoplasm patients

Abstract

AbstractBackground: DNA hypermethylation and instability due to inactivation mutations in Ten–eleven translocation 2 (TET2) is a key biomarker of hematological malignancies. This study aims at characterizing two intronic noncanonical splice‐site variants, c.3954+5_3954+8delGTTT and c.3954+5G>A.Methods: We used in silico prediction tools, reverse transcription (RT)‐PCR, and Sanger sequencing on blood/bone marrow‐derived RNA specimens to determine the aberrant splicing.Results: In silico prediction of both variants exhibited reduced splicing strength at the TET2 intron 7 splicing donor site. RT‐PCR and Sanger sequencing identified a 62‐bp deletion at the exon 7, producing a frameshift mutation, p.Cys1298*.Conclusion: This study provides functional evidence for two intronic TET2 variants that cause alternative splicing and frameshift mutation.