20.500.12556/DiRROS-15458 Identification of spliceogenic variants beyond canonical GT-AG splice sites in hereditary cancer genes Pathogenic/likely pathogenic variants in susceptibility genes that interrupt RNA splicing are a well-documented mechanism of hereditary cancer syndromes development. However, if RNA studies are not performed, most of the variants beyond the canonical GT-AG splice site are characterized as variants of uncertain significance (VUS). To decrease the VUS burden, we have bioinformatically evaluated all novel VUS detected in 732 consecutive patients tested in the routine genetic counseling process. Twelve VUS that were predicted to cause splicing defects were selected for mRNA analysis. Here, we report a functional characterization of 12 variants located beyond the first two intronic nucleotides using RNAseq in APC, ATM, FH, LZTR1, MSH6, PALB2, RAD51C, and TP53 genes. Based on the analysis of mRNA, we have successfully reclassified 50% of investigated variants. 25% of variants were downgraded to likely benign, whereas 25% were upgraded to likely pathogenic leading to improved clinical management of the patient and the family members. hereditary cancer RNA sequencing spliceogenic dedni raki sekvencioniranje RNA spajanje geni true false true MDPI Angleški jezik Slovenski jezik by Authors Neznano 2022-09-07 03:37:44 2022-09-07 09:10:23 2022-09-08 03:36:07 0000-00-00 00:00:00 2022 0 0 Nasl. z nasl. zaslona; Opis vira z dne 6. 7. 2022; str. 7446-1-7446-14 no. 13 Vol. 23 2022 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2022-07-04 602 1422-0067 10.3390/ijms23137446 114023427 https://www.mdpi.com/1422-0067/23/13/7446 1 e9d5887c-2e3c-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20443 RAZ_Setrajcic_Dragos_Vita_2022.pdf RAZ_Setrajcic_Dragos_Vita_2022.pdf 1 474DFF0799FF629B33541DF287F153D6 379c2f1e7ab030eb289de3b308a16b1f40f9e3ce9ae696112559d8b951a4e713 dd289fc5-2e88-11ed-bea5-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=20454 Onkološki inštitut Ljubljana 0 0 0