{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:26:12Z","timestamp":1782271572708,"version":"3.54.5"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011958","name":"Independent Research Fund Denmark","doi-asserted-by":"publisher","award":["10.46540\/3188-00032B"],"award-info":[{"award-number":["10.46540\/3188-00032B"]}],"id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011958","name":"Independent Research Fund Denmark","doi-asserted-by":"publisher","award":["R337-A19545"],"award-info":[{"award-number":["R337-A19545"]}],"id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011958","name":"Independent Research Fund Denmark","doi-asserted-by":"publisher","award":["A5478"],"award-info":[{"award-number":["A5478"]}],"id":[{"id":"10.13039\/501100011958","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"the Danish Cancer Society","doi-asserted-by":"publisher","award":["10.46540\/3188-00032B"],"award-info":[{"award-number":["10.46540\/3188-00032B"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"the Danish Cancer Society","doi-asserted-by":"publisher","award":["R337-A19545"],"award-info":[{"award-number":["R337-A19545"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008363","name":"the Danish Cancer Society","doi-asserted-by":"publisher","award":["A5478"],"award-info":[{"award-number":["A5478"]}],"id":[{"id":"10.13039\/100008363","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Odense University Hospital Fund for Pre-graduate Stipends","award":["10.46540\/3188-00032B"],"award-info":[{"award-number":["10.46540\/3188-00032B"]}]},{"name":"the Odense University Hospital Fund for Pre-graduate Stipends","award":["R337-A19545"],"award-info":[{"award-number":["R337-A19545"]}]},{"name":"the Odense University Hospital Fund for Pre-graduate Stipends","award":["A5478"],"award-info":[{"award-number":["A5478"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Gene variants of unknown significance (VUSs) present a challenge in genetic counselling. The primary aim of this study was to describe the spectrum of genetic findings in a cohort of 5923 Danish patients with suspected predisposition to hereditary breast and\/or ovarian cancer, with a focus on classifying gene variants and investigating their distribution. Methods: The gene variants were classified using the American College of Medical Genetics (ACMG) guidelines as well as gene-specific guidelines where applicable. The identified VUSs were further examined through association analysis, comparison of the frequencies in this Danish population to those in the Swedish population using gnomAD 2.1, and splice analysis using RNA sequencing. Results: Of 167 variants that were clinically classified as VUSs prior to this research study, 38 (22.8%) were either up- or downgraded based on the guidelines that were used. We found that 630 patients (10.6%) carried a likely pathogenic or pathogenic variant, mainly in BRCA1 (31.9%) and BRCA2 (26.0%). VUSs were carried by 1606 (27.1%) patients, mainly in BARD1 (27.6%) and ATM (19.3%). Our association study assigned criteria for 10 gene variants, while our splice analysis assigned criteria for 3 gene variants but did not reclassify the variants. Conclusions: A total of 22.8% of the 167 variants that were observed in this study and which were previously classified as VUSs in a clinical setting were reclassified in this study. In total, 10.6% of the patients with a suspected predisposition to hereditary breast and\/or ovarian cancer carried a likely pathogenic or pathogenic variant. The high incidence of VUSs observed in this study reflects the challenges faced in the daily clinical setting.<\/jats:p>","DOI":"10.3390\/cancers17111819","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T09:47:34Z","timestamp":1748512054000},"page":"1819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Classification of Gene Variants in a Danish Population with Suspected Predisposition to Hereditary Breast and\/or Ovarian Cancer"],"prefix":"10.3390","volume":"17","author":[{"given":"Anne K.","family":"Munch","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth S.","family":"Feldner","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H.","family":"B\u00e6kgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mie B.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naja","family":"Slemming-Adamsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2091-813X","authenticated-orcid":false,"given":"Desir\u00e9e S.","family":"Boonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanna B.","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Aarhus University Hospital, Brendstrupg\u00e5rdsvej 21C, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-8040","authenticated-orcid":false,"given":"Inge S.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics, Aalborg University Hospital, Reberbansgade 15, 9000 Aalborg, Denmark"},{"name":"Department of Clinical Medicine, Aalborg University, Selma Lagerl\u00f8fsvej 249, 9260 Gistrup, Denmark"},{"name":"Clinical Cancer Research Center, Sdr. Skovvej 15, 9000 Aalborg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-2653","authenticated-orcid":false,"given":"Thomas V. O.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B A, 2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thorkild","family":"Terkelsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Aarhus University Hospital, Brendstrupg\u00e5rdsvej 21C, 8200 Aarhus, Denmark"},{"name":"Department of Biomedicine, Aarhus University, H\u00f8egh-Guldbergsgade 10, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-5933","authenticated-orcid":false,"given":"Mark","family":"Burton","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark"},{"name":"Clinical Genome Center, Odense University Hospital, University of Southern Denmark, J.B. Winslows Vej 15, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7824-2080","authenticated-orcid":false,"given":"Susanne E.","family":"Boonen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mads","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winslows Vej 4, Entrance 24, 5000 Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark"},{"name":"Clinical Genome Center, Odense University Hospital, University of Southern Denmark, J.B. Winslows Vej 15, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"ref_1","unstructured":"(2024, December 17). Information About the Danish Breast Cancer Screening Programme. 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