Whole genome germline sequencing: Its role in general health screening in family practice, the first study in the UK.

10510 Background: Whole genome sequencing (WGS) is now possible due to improvements in next generation sequencing technology. This gives the opportunity to incorporate genetic data into family practice health screening. The fulfilment of the potential of WGS lies in its future implementation into family practice. This study aimed to set up a model pathway to undertake WGS for actionable findings and assess its potential role in enhancing health screening. Methods: A pilot study comprised of 100 healthy participants from 2020-2022, recruited from a family practice, consented to routine baseline blood tests, cardiac assessment (ECG and echocardiogram), abdominopelvic ultrasound, all performed at the practice. Review of past medical, and family history was done from electronic health records (EHR). Germline genetic testing consisted of 84 cancer and 77 cardiac genes and whole genome sequencing (566 actionable genes reported), including higher penetrance monogenic mutations, recessive carrier alterations and pharmacogenomics. A multidisciplinary clinical team reviewed integrated results through an iterative process, which fed back to participants. Results: Twenty of 100 individuals (20%) had an actionable genetic variant in either cancer (10 individuals), thrombophilia (8) or cardiac rhythm disorder genes (2). Eighty percent of the participants had a variant in an autosomal recessive gene. Pharmacogenomics results yielded significant variants in 30%. Conclusions: The majority of patients had a significant change in management for themselves or their families. Whole genome sequencing as part of health screening in family practice is feasible and is likely to have significant beneficial health management implications. This study is the first of its kind in family practice and shows how this can be implemented.