BARD1 was first reported in relation to Ovarian Cancer in 1998 (Thai et al., PMID: 9425226). BARD1 was proposed to be linked to ovarian cancer due to its relationship with breast cancer and an early case-control study (PMID: 26720728). The mechanism of pathogenicity was proposed to be via BRCA1 binding and subsequent loss of DNA damage response. BARD1-related cancer predisposition MONDO:0700267 is characterized by a susceptibility to breast cancer with emerging evidence suggesting the association of other cancer types including neuroblastoma. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, we did a split curation for BARD1-related ovarian cancer predisposition given evidence to dispute or refute. The prior curation in 2017 was Limited. For ovarian cancer, 1 variant has been reported in 1 proband in 1 study (PMID: 9425226), no other clear disease causing variants could be identified. This gene-disease relationship has been studied in at least 8 case-control studies at the aggregate variant level and 1 case-control study (PMID:15342711) at the single variant level. Of these studies, one study reports an association (PMID: 26720728) while 4 report no association (non-significant Odds Ratio), and another 3 reported that despite evaluating BARD1, no associated variants were identified in any cases (PMIDs: 31036035, 15342711, 29020732). In summary, the evidence supporting the relationship between BARD1 and autosomal dominant hereditary ovarian cancer has been disputed and no valid evidence remains to support the claim. More evidence is needed to entirely refute the role BARD1 plays in this disease. This re-curation as disputed was approved by the ClinGen Hereditary Cancer GCEP on 04/26/2024 (SOP Version 10). As a result of this re-evaluation, the overall classification changed from Limited to Disputed.
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