Professor Lina Basel-Salmon is a specialist in pediatrics and medical genetics. She serves as Director of Research and Innovation in Genomic Medicine at Maccabi Healthcare Services and is a Full Professor at Tel Aviv University, where she holds the Gabriel Pinkas Chair for the Prevention and Diagnosis of Congenital Anomalies. Her work spans the diagnostics of rare diseases, genomic variant interpretation in the clinical setting, and population-based screening. She has led the discovery of more than 20 novel gene-disease associations and has authored over 200 publications. She has delivered educational workshops in numerous countries and led the establishment of the genetic counseling training program at Tel Aviv University
Professor Basel-Salmon is a member of the Scientific Advisory Board of WHO/Europe, the Strategic Committee of the European Society of Human Genetics, and the Multistakeholder Advisory Board of the European Rare Diseases Research Alliance. Her previous leadership roles include serving as Head of the Israeli Society of Medical Genetics and National Coordinator of Orphanet Israel. At Maccabi Healthcare Services, she focuses on integrating genomic technologies into clinical care, developing population-level genomic strategies, and translating scientific advances into practical healthcare solutions.
Population-Scale Return of Secondary Findings: Yield, Challenges, and Implementation Lessons
Psifas, the Israeli National Genomic Medicine Initiative, conducts population-based whole-genome sequencing and returns medically actionable secondary findings (SFs) to participants through affiliated clinical genetics services. Among 58,003 adults who underwent whole-genome sequencing, pathogenic or likely pathogenic (P/LP) SFs in the 81 genes included in the ACMG SF v3.2 list were identified in 1,708 participants (2.95%), with 49.8% of the findings occurring in CDC Tier 1 genes. Clinical confirmation was successful in 99.4% of cases. Of the carriers, 789 completed genetic counselling, 81.7% of whom had not previously been aware of their genetic risk. Prior awareness differed markedly by disease category: 43% of participants with cancer-related variants were already aware of the finding, compared with only 8% of those with cardiovascular findings. The three BRCA1/BRCA2 founder variants accounted for 75% of all BRCA1/BRCA2 findings. The return of results process identified important potential sources of misinterpretation: i) Phenotype-informed clinical review, incorporating additional clinically derived ACMG/AMP evidence, resulted in the downgrading of 29 initially P/LP classifications to variants of uncertain significance; ii) Most counselled participants with TP53 findings had no supporting personal or family history, raising the possibility that these variants reflect clonal hematopoiesis. We adopted a two-stage documentation model in which research findings are communicated to clinical genetics services as preliminary and entered into the permanent medical record only after confirmation in a certified clinical laboratory and phenotype-informed interpretation.
Population-scale return of SFs is feasible but requires confirmatory testing, phenotype-informed interpretation, and scalable clinical infrastructure to maximize clinical benefit while minimizing potential harm.