Project 466707

Reading entire DNA sequences of individuals provides a comprehensive view of the unique genetic variation that contributes to a breath of diseases, from rare genetic disorders to common cancers. A common type of variation, missense variants, represent single changes of the genetic code that often negatively impact proteins that DNA codes for and cause harmful effects. However, distinguishing missense variants that cause disease from the majority that have no consequence remains a challenge. This study aims to develop a new approach for determining if rare variants are associated with human disease.An area that has not been investigated is the observed overlap between germline DNA variants that cause genetic disorders and acquired somatic variants that cause cancer. Many mutations in cancer genes are associated with rare genetic disorders when they are found in germline DNA. By comparing information from various genetic and cancer database, this can be explored further to identify any relationships. A computation tool will first be established to extract cancer missense variants, the Cancer Hotspots and COSMIC databases, that are shared with genetic disorder-related germline DNA variants reported in ClinVar. Using this data, accompanied by additional parameters, a statistical model will be developed and tested across clinical datasets to estimate the probability of a novel missense variant being disease-causing. The results from this study will introduce additional criteria for classifying missense variants for improving clinical diagnosis to allow better treatment and health outcomes. It will also create opportunities for experimental studies to investigate the overlap of germline/cancer variants and give special insights into human genetics.