Reclassification of clinical exome data leads to significant clinical assessment changes in almost half of the patients

Authors : Umut Arda BAYRAKTAR, Feride İffet ŞAHİN, Mert POLAT, Yunus Kasım TERZİ

Pages : 1072-1080

Doi:10.17826/cumj.1316760

View : 19 | Download : 43

Publication Date : 2023-09-30

Article Type : Research Paper

Abstract :Purpose: With the global accumulation of genetic/clinical data, we are understanding the clinical significance of the reclassification of pathogenicity for gene variants. We hypothesized that this evolution in classificationinsert ignore into journalissuearticles values(s); may cause clinically-relevant discrepancies in the genetic risk assessment of subjects. In this study, we sought to reclassify the clinical exome sequence insert ignore into journalissuearticles values(CES); data of our patients to assess whether these changes would have clinical significance. Materials and Methods: The study included CES data of 23 cases diagnosed with cancer or familial cancer predisposition. The variants were first classified in 2020 and then reclassified a year after based on the ACMG database. Chart reviews were performed to record clinical history and interventions. Results: In the first classification of CES data, a total of 80 variants were identified as being not benign insert ignore into journalissuearticles values(26 likely pathogenic/pathogenic and 54 variants of undetermined significance insert ignore into journalissuearticles values(VUS););. The clinical significance of fifteen variants insert ignore into journalissuearticles values(19%); changed after reclassification in 10 patients insert ignore into journalissuearticles values(43%);. The only upgraded variant was the c.9097 dup in exon 23 of BRCA2 gene insert ignore into journalissuearticles values(likely pathogenic to pathogenic);. Fourteen variants were downgraded at reanalysis in 9 patients: from pathogenic to likely pathogenic insert ignore into journalissuearticles values(2 variants);, pathogenic to VUS insert ignore into journalissuearticles values(2);, likely pathogenic to VUS insert ignore into journalissuearticles values(4);, and VUS to benign insert ignore into journalissuearticles values(6);. Conclusion: Considering that the clinical significance of CES data changed due to reclassification in almost half of the studied patients, we believe genetic variant-related data should be assessed at regular intervals, regardless of follow-up status in the clinic.
Keywords : Kanser, klinik ekzom sekanslama, olası patojenik patojenik varyantlar