Reclassification of <i>BRCA1/2</i> gene variants of uncertain significance according to American College of Medical Genetics and Genomics guidelines

Purpose: Mutations in BRCA1 and BRCA2 genes are associated with increased risk of breast cancer.Variants identified in BRCA1/2 are classified as pathogenic, benign, or variants of uncertain significance (VUS).Regular reassessment of VUS is essential to ensure accurate patient risk identification.Materials and Methods: In this study, we analyzed the reclassification of BRCA1/2 gene variants in 1,652 samples from 2020 to 2022, following the American College of Medical Genetics and Genomics guidelines.Blood samples obtained from patients were sequenced and BRCA1/2 sequences were assessed to identify VUS.Results: A total of 93 VUS were identified, of which 30 (32.25%) were reclassified.The reclassified variants included 10 benign, 3 benign/likely benign, 6 likely benign, 1 benign/uncertain significance, 7 likely benign/uncertain significance, 1 likely pathogenic/uncertain significance, 1 likely pathogenic, and 1 pathogenic.Reanalysis using public databases, such as ClinVar plays a critical role in variant interpretation.Additionally, regular data updates and institution-specific reanalysis protocols are essential for maintaining accuracy.The high reclassification rate observed in this study can be attributed to advancements in data analysis technology.Conclusion: Regular reanalysis of BRCA1/2 variant is critical for personalized risk assessment and treatment.Institutions should implement systems for periodic reanalysis and incorporate the latest data for improved diagnostic accuracy.Future research should focus on larger sample sizes and foster collaboration to achieve global standardization of gene variant interpretation, contributing to the development of personalized treatment strategies and overall medical advancement.