We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). Methods: Two large databases of individuals fulfilling NF2 criteria (n=1361) and those tested for NF2 variants with criteria short of diagnosis (n=1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the specificity with regard to refuted diagnosis. Results: There was no evidence for usefulness of old criteria 'glioma' or 'neurofibroma'. 'Ependymoma' had 100% specificity and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced specificity (80%). Siblings as a firstdegree-relative, without an affected parent, had 0% specificity. All three individuals with a unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with a unilateral VS plus ≥2 non-dermal schwannomas reduced specificity to 67%. Conclusion: The present study has confirmed important deficiencies in NF2 diagnostic criteria. The term 'glioma' should be dropped and replaced by 'ependymoma'. Similarly 'neurofibroma' should be removed. Dropping 'sibling' from first-degreerelatives should be considered and testing of LZTR1 should be recommended for unilateral VS.

Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained.This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately. K E Y W O R D SBRCA, genetic risk, homologous recombination, mismatch repair, ovarian cancer, polygenic risk score, SNPs