{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T14:38:49Z","timestamp":1787841529769,"version":"build-2784847793"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1007\/s12282-026-01886-9","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T08:15:33Z","timestamp":1783152933000},"page":"1118-1128","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional characterization of BRCA2 variants of uncertain significance identified in Korean breast cancer patients"],"prefix":"10.1007","volume":"33","author":[{"given":"Ah Reum","family":"Lim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Pil","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Jin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong Hwa","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9665-062X","authenticated-orcid":false,"given":"Soohyeon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"1886_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209\u201349. https:\/\/doi.org\/10.3322\/caac.21660.","journal-title":"CA Cancer J Clin"},{"key":"1886_CR2","doi-asserted-by":"publisher","unstructured":"Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science (1979). 1994;265:2088\u201390. https:\/\/doi.org\/10.1126\/science.8091231","DOI":"10.1126\/science.8091231"},{"key":"1886_CR3","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/s0092-8674(02)00615-3","volume":"108","author":"AR Venkitaraman","year":"2002","unstructured":"Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 2002;108:171\u201382. https:\/\/doi.org\/10.1016\/s0092-8674(02)00615-3.","journal-title":"Cell"},{"key":"1886_CR4","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/nature01230","volume":"420","author":"L Pellegrini","year":"2002","unstructured":"Pellegrini L, Yu DS, Lo T, Anand S, Lee M, Blundell TL, et al. Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature. 2002;420:287\u201393. https:\/\/doi.org\/10.1038\/nature01230.","journal-title":"Nature"},{"key":"1886_CR5","doi-asserted-by":"publisher","first-page":"31941","DOI":"10.1074\/jbc.272.51.31941","volume":"272","author":"AK Wong","year":"1997","unstructured":"Wong AK, Pero R, Ormonde PA, Tavtigian SV, Bartel PL. RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene BRCA2. J Biol Chem. 1997;272:31941\u20134. https:\/\/doi.org\/10.1074\/jbc.272.51.31941.","journal-title":"J Biol Chem"},{"key":"1886_CR6","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nature09399","volume":"467","author":"RB Jensen","year":"2010","unstructured":"Jensen RB, Carreira A, Kowalczykowski SC. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature. 2010;467:678\u201383. https:\/\/doi.org\/10.1038\/nature09399.","journal-title":"Nature"},{"key":"1886_CR7","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/nrc1457","volume":"4","author":"N Turner","year":"2004","unstructured":"Turner N, Tutt A, Ashworth A. Hallmarks of \u2018BRCAness\u2019 in sporadic cancers. Nat Rev Cancer. 2004;4:814\u20139. https:\/\/doi.org\/10.1038\/nrc1457.","journal-title":"Nat Rev Cancer"},{"key":"1886_CR8","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nature03445","volume":"434","author":"H Farmer","year":"2005","unstructured":"Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917\u201321. https:\/\/doi.org\/10.1038\/nature03445.","journal-title":"Nature"},{"key":"1886_CR9","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nrc.2015.21","volume":"16","author":"CJ Lord","year":"2016","unstructured":"Lord CJ, Ashworth A. BRCAness revisited. Nat Rev Cancer. 2016;16:110\u201320. https:\/\/doi.org\/10.1038\/nrc.2015.21.","journal-title":"Nat Rev Cancer"},{"key":"1886_CR10","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3389\/fonc.2018.00016","volume":"8","author":"S Mylavarapu","year":"2018","unstructured":"Mylavarapu S, Das A, Roy M. Role of BRCA Mutations in the Modulation of Response to Platinum Therapy. Front Oncol. 2018;8:16. https:\/\/doi.org\/10.3389\/fonc.2018.00016.","journal-title":"Front Oncol"},{"key":"1886_CR11","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1200\/jco.2013.53.2820","volume":"32","author":"AP Finch","year":"2014","unstructured":"Finch AP, Lubinski J, M\u00f8ller P, Singer CF, Karlan B, Senter L, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014;32:1547\u201353. https:\/\/doi.org\/10.1200\/jco.2013.53.2820.","journal-title":"J Clin Oncol"},{"key":"1886_CR12","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1001\/jama.2017.7112","volume":"317","author":"KB Kuchenbaecker","year":"2017","unstructured":"Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017;317:2402\u201316. https:\/\/doi.org\/10.1001\/jama.2017.7112.","journal-title":"JAMA"},{"key":"1886_CR13","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1056\/NEJMoa1706450","volume":"377","author":"M Robson","year":"2017","unstructured":"Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377:523\u201333. https:\/\/doi.org\/10.1056\/NEJMoa1706450.","journal-title":"N Engl J Med"},{"key":"1886_CR14","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1056\/NEJMoa1802905","volume":"379","author":"JK Litton","year":"2018","unstructured":"Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gon\u00e7alves A, Lee KH, et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018;379:753\u201363. https:\/\/doi.org\/10.1056\/NEJMoa1802905.","journal-title":"N Engl J Med"},{"key":"1886_CR15","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1002\/cncr.31307","volume":"124","author":"AA Turk","year":"2018","unstructured":"Turk AA, Wisinski KB. PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside. Cancer. 2018;124:2498\u2013506. https:\/\/doi.org\/10.1002\/cncr.31307.","journal-title":"Cancer"},{"key":"1886_CR16","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1002\/humu.23626","volume":"39","author":"AN Abou Tayoun","year":"2018","unstructured":"Abou Tayoun AN, Pesaran T, DiStefano MT, Oza A, Rehm HL, Biesecker LG, et al. Recommendations for interpreting the loss of function PVS1 ACMG\/AMP variant criterion. Hum Mutat. 2018;39:1517\u201324. https:\/\/doi.org\/10.1002\/humu.23626.","journal-title":"Hum Mutat"},{"key":"1886_CR17","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med"},{"key":"1886_CR18","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.jncc.2022.12.001","volume":"3","author":"SM Wang","year":"2023","unstructured":"Wang SM. A global perspective on the ethnic-specific BRCA variation and its implication in clinical application. J Natl Cancer Cent. 2023;3:14\u201320. https:\/\/doi.org\/10.1016\/j.jncc.2022.12.001.","journal-title":"J Natl Cancer Cent"},{"key":"1886_CR19","doi-asserted-by":"publisher","first-page":"8485","DOI":"10.1038\/s41598-021-87792-w","volume":"11","author":"JH Kim","year":"2021","unstructured":"Kim JH, Park S, Park HS, Park JS, Lee ST, Kim SW, et al. Analysis of BRCA1\/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study. Sci Rep. 2021;11:8485. https:\/\/doi.org\/10.1038\/s41598-021-87792-w.","journal-title":"Sci Rep"},{"key":"1886_CR20","doi-asserted-by":"publisher","first-page":"411","DOI":"10.5468\/ogs.2019.62.6.411","volume":"62","author":"JH Seo","year":"2019","unstructured":"Seo JH, Jeong SY, Kim MS, Kang JH, Paik ES, Lee YY, et al. Prevalence and oncologic outcomes of BRCA1\/2 mutation and variant of unknown significance in epithelial ovarian carcinoma patients in Korea. Obstet Gynecol Sci. 2019;62:411\u20139. https:\/\/doi.org\/10.5468\/ogs.2019.62.6.411.","journal-title":"Obstet Gynecol Sci"},{"key":"1886_CR21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13045-020-01010-0","volume":"14","author":"Y Liu","year":"2021","unstructured":"Liu Y, Wang H, Wang X, Liu J, Li J, Wang X, et al. Prevalence and reclassification of BRCA1 and BRCA2 variants in a large, unselected Chinese Han breast cancer cohort. J Hematol Oncol. 2021;14:18. https:\/\/doi.org\/10.1186\/s13045-020-01010-0.","journal-title":"J Hematol Oncol"},{"key":"1886_CR22","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1158\/2159-8290.Cd-21-1064","volume":"12","author":"KH Park","year":"2022","unstructured":"Park KH, Choi JY, Lim AR, Kim JW, Choi YJ, Lee S, et al. Genomic Landscape and Clinical Utility in Korean Advanced Pan-Cancer Patients from Prospective Clinical Sequencing: K-MASTER Program. Cancer Discov. 2022;12:938\u201348. https:\/\/doi.org\/10.1158\/2159-8290.Cd-21-1064.","journal-title":"Cancer Discov"},{"key":"1886_CR23","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1126\/science.aam7344","volume":"355","author":"CJ Lord","year":"2017","unstructured":"Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Sci (1979). 2017;355:1152\u20138. https:\/\/doi.org\/10.1126\/science.aam7344.","journal-title":"Sci (1979)"},{"key":"1886_CR24","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1002\/humu.22455","volume":"35","author":"RK Olsen","year":"2014","unstructured":"Olsen RK, Br\u00f8ner S, Sabaratnam R, Doktor TK, Andersen HS, Bruun GH, et al. The ETFDH c.158A\u2009>\u2009G variation disrupts the balanced interplay of ESE- and ESS-binding proteins thereby causing missplicing and multiple Acyl-CoA dehydrogenation deficiency. Hum Mutat. 2014;35:86\u201395. https:\/\/doi.org\/10.1002\/humu.22455.","journal-title":"Hum Mutat"},{"key":"1886_CR25","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1002\/humu.22129","volume":"33","author":"A El-Seedy","year":"2012","unstructured":"El-Seedy A, Girodon E, Norez C, Pajaud J, Pasquet MC, de Becdeli\u00e8vre A, et al. CFTR mutation combinations producing frequent complex alleles with different clinical and functional outcomes. Hum Mutat. 2012;33:1557\u201365. https:\/\/doi.org\/10.1002\/humu.22129.","journal-title":"Hum Mutat"},{"key":"1886_CR26","doi-asserted-by":"publisher","first-page":"8988","DOI":"10.1073\/pnas.94.17.8988","volume":"94","author":"ME Moynahan","year":"1997","unstructured":"Moynahan ME, Jasin M. Loss of heterozygosity induced by a chromosomal double-strand break. Proc Natl Acad Sci U S A. 1997;94:8988\u201393. https:\/\/doi.org\/10.1073\/pnas.94.17.8988.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1886_CR27","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s10549-015-3377-4","volume":"151","author":"E Kang","year":"2015","unstructured":"Kang E, Seong MW, Park SK, Lee JW, Lee J, Kim LS, et al. The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study. Breast Cancer Res Treat. 2015;151:157\u201368. https:\/\/doi.org\/10.1007\/s10549-015-3377-4.","journal-title":"Breast Cancer Res Treat"},{"key":"1886_CR28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s10689-012-9578-7","volume":"12","author":"SA Han","year":"2013","unstructured":"Han SA, Kim SW, Kang E, Park SK, Ahn SH, Lee MH, et al. The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study. Fam Cancer. 2013;12:75\u201381. https:\/\/doi.org\/10.1007\/s10689-012-9578-7.","journal-title":"Fam Cancer"},{"key":"1886_CR29","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/humu.21627","volume":"33","author":"NM Lindor","year":"2012","unstructured":"Lindor NM, Guidugli L, Wang X, Vall\u00e9e MP, Monteiro AN, Tavtigian S, et al. A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). Hum Mutat. 2012;33:8\u201321. https:\/\/doi.org\/10.1002\/humu.21627.","journal-title":"Hum Mutat"},{"key":"1886_CR30","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1136\/jmedgenet-2018-105565","volume":"55","author":"JS Lee","year":"2018","unstructured":"Lee JS, Oh S, Park SK, Lee MH, Lee JW, Kim SW, et al. Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort. J Med Genet. 2018;55:794\u2013802. https:\/\/doi.org\/10.1136\/jmedgenet-2018-105565.","journal-title":"J Med Genet"},{"key":"1886_CR31","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1002\/humu.22478","volume":"35","author":"L Guidugli","year":"2014","unstructured":"Guidugli L, Carreira A, Caputo SM, Ehlen A, Galli A, Monteiro AN, et al. Functional assays for analysis of variants of uncertain significance in BRCA2. Hum Mutat. 2014;35:151\u201364. https:\/\/doi.org\/10.1002\/humu.22478.","journal-title":"Hum Mutat"},{"key":"1886_CR32","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1158\/0008-5472.Can-12-2081","volume":"73","author":"L Guidugli","year":"2013","unstructured":"Guidugli L, Pankratz VS, Singh N, Thompson J, Erding CA, Engel C, et al. A classification model for BRCA2 DNA binding domain missense variants based on homology-directed repair activity. Cancer Res. 2013;73:265\u201375. https:\/\/doi.org\/10.1158\/0008-5472.Can-12-2081.","journal-title":"Cancer Res"},{"key":"1886_CR33","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1002\/humu.22150","volume":"33","author":"GA Millot","year":"2012","unstructured":"Millot GA, Carvalho MA, Caputo SM, Vreeswijk MP, Brown MA, Webb M, et al. A guide for functional analysis of BRCA1 variants of uncertain significance. Hum Mutat. 2012;33:1526\u201337. https:\/\/doi.org\/10.1002\/humu.22150.","journal-title":"Hum Mutat"},{"key":"1886_CR34","doi-asserted-by":"publisher","first-page":"3108","DOI":"10.1200\/JCO.2019.37.15_suppl.3108","volume":"37","author":"S Chevrier","year":"2019","unstructured":"Chevrier S, Desmoulins I, Favier L, Ghiringhelli F, Bengrine L, Arnould L, et al. Prediction of olaparib sensitivity for variants of unknown significance in homologous repair genes. J Clin Oncol. 2019;37:3108. https:\/\/doi.org\/10.1200\/JCO.2019.37.15_suppl.3108.","journal-title":"J Clin Oncol"},{"key":"1886_CR35","doi-asserted-by":"publisher","first-page":"1053035","DOI":"10.3389\/fonc.2022.1053035","volume":"12","author":"E De Paolis","year":"2022","unstructured":"De Paolis E, Paris I, Tilocca B, Roncada P, Foca L, Tiberi G, et al. Assessing the pathogenicity of BRCA1\/2 variants of unknown significance: Relevance and challenges for breast cancer precision medicine. Front Oncol. 2022;12:1053035. https:\/\/doi.org\/10.3389\/fonc.2022.1053035.","journal-title":"Front Oncol"}],"container-title":["Breast Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-026-01886-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12282-026-01886-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-026-01886-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T13:58:29Z","timestamp":1787839109000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12282-026-01886-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,4]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["1886"],"URL":"https:\/\/doi.org\/10.1007\/s12282-026-01886-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8617436\/v1","asserted-by":"object"}]},"ISSN":["1340-6868","1880-4233"],"issn-type":[{"value":"1340-6868","type":"print"},{"value":"1880-4233","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,4]]},"assertion":[{"value":"16 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Institutional Review Board of Korea University Anam Hospital (2017AN0401) and was conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. The manuscript does not contain individual, identifiable patient data.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}]}}