by American College of Medical Genetics and Genomics

Proband with personal and family history of breast cancer and RAD51D germline pathogenic variant. A 54-year-old woman presented to the clinic with a personal history of triple-negative breast cancer and a maternal family history of breast cancer. She was tested through a commercial laboratory who identified a pathogenic variant in RAD51D. Credit:Genetics in Medicine(2025). DOI: 10.1016/j.gim.2025.101557

The American College of Medical Genetics and Genomics (ACMG) haspublisheda new clinical practice resource, "Management of Individuals with Heterozygous Germline Pathogenic Variants in RAD51C, RAD51D, and BRIP1: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)," in its journal,Genetics in Medicine. The publication provides evidence-based guidance for clinicians managing individuals with heterozygous germline pathogenic variants (GPVs) in RAD51C, RAD51D, and BRIP1, genes associated with increased cancer risks, particularly ovarian and breast cancers.

This practice resource provides guidance for clinicians caring for individuals with these moderate-penetrancecancersusceptibility variants, offering evidence-based recommendations on personalizedrisk assessment, surveillance, and risk-reducing interventions.

"Variants in RAD51C, RAD51D, and BRIP1 are increasingly being identified through multi-gene panel testing," said Joanne Ngeow, MBBS, MPH, Senior Consultant and Head of Cancer Genetics Service, National Cancer Center Singapore, Associate Professor, Nanyang Technological University, Singapore's Lee Kong Chian School of Medicine, and lead author of the practice resource.

"Our guidance helps clinicians interpret these findings, communicate cancer risks to patients, and make informed decisions on interventions such as risk-reducing surgery and enhanced surveillance strategies."

Key recommendations include:

The practice resource also highlights the importance of personalized risk assessments that integratefamily history, polygenic risk scores, and other clinical factors, as well as the need for genetic counseling to guide patients and families through testing, risk management, and reproductive planning. It represents an important step in translating emerging research into clinical practice, ensuring that new genetic insights lead to actionable care for patients today, even as the science continues to evolve.

"This resource reflects ACMG's commitment to providing clinicians with actionable, evidence-based guidance. By developing this clinical resource through an international workgroup, we can better support individuals with RAD51C, RAD51D, and BRIP1 variants in understanding their cancer risks and taking proactive steps to manage their health.

"Resources like this are essential for helpingcliniciansapply rapidly advancing research in real-world care and for ensuring we continue to move forward, even as new data emerge," said Helen Hanson, MD, Consultant and Associate Professor Clinical Cancer Genetics, Royal Devon University NHS Foundation Trust and University of Exeter Medical School, and senior author of the practice resource.

More information: Joanne Ngeow et al, Management of individuals with heterozygous germline pathogenic variants in RAD51C, RAD51D, and BRIP1: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG), Genetics in Medicine (2025). DOI: 10.1016/j.gim.2025.101557 Journal information: Genetics in Medicine

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American College of Medical Genetics and Genomics