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

: DNA hypermethylation and instability due to inactivation mutations in Ten-eleven translocation 2 () 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. : We used prediction tools, reverse transcription (RT)-PCR, and Sanger sequencing on blood/bone marrow-derived RNA specimens to determine the aberrant splicing. : prediction of both variants exhibited reduced splicing strength at the 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*. : This study provides functional evidence for two intronic variants that cause alternative splicing and frameshift mutation.