Pathogenic variants in PALB2 is associated with an increased risk of breast, ovarian and pancreatic cancer. In our case-control study of more than 15,000 women from two multi-ethnic South East Asian populations (Malaysia and Singapore), we found that PALB2 carriers have a 5 fold increased risk of breast cancer compared to healthy individuals. Notably, many of the variants identified in this understudied population are novel and our functional analyses of rare missense variants indicate that only a minority are associated with an increased risk to breast cancer.  Together, this study adds to the evidence base that PALB2 is clinically relevant across diverse populations. (By Professor Datin Paduka and Dr Teo Soo Hwang, https://jmg.bmj.com/content/early/2021/04/01/jmedgenet-2020-107471 )