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Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including <jats:italic>BRCA<\/jats:italic> impairment, there is no clear evidence of the relationship between <jats:italic>RAD51D<\/jats:italic> variants and the risk of sarcoma development.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4\u2009years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of <jats:italic>RAD51D<\/jats:italic> c.904-2A\u2009&gt;\u2009T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the <jats:italic>RAD51D<\/jats:italic> splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of <jats:italic>RAD51D<\/jats:italic> with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3\u2032-end of intron 9 of <jats:italic>RAD51D<\/jats:italic>. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered <jats:italic>RAD51D<\/jats:italic>, this case provided novel evidence for the relationship of a <jats:italic>RAD51D<\/jats:italic> splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of <jats:italic>RAD51D<\/jats:italic> c.904-2A\u2009&gt;\u2009T as a potential predisposing factor for malignant tumors, including leiomyosarcoma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of <jats:italic>RAD51D<\/jats:italic> as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and\/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline <jats:italic>RAD51D<\/jats:italic> splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13053-021-00205-x","type":"journal-article","created":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T09:02:41Z","timestamp":1638003761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A\u2009&gt;\u2009T: a case report"],"prefix":"10.1186","volume":"19","author":[{"given":"Mashu","family":"Futagawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4919-3483","authenticated-orcid":false,"given":"Hideki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Kochi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusaku","family":"Urakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reimi","family":"Sogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumino","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Okazawa-Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ennishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunori","family":"Shinozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yanai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hirasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,27]]},"reference":[{"issue":"8","key":"205_CR1","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1016\/j.semcdb.2011.07.019","volume":"22","author":"N Suwaki","year":"2011","unstructured":"Suwaki N, Klare K, Tarsounas M. 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Cancer genome profiling was performed as a part of general practice in cancer genome medicine facilitated by the alliance hospitals in Japan. Genomic analyses and interpretations were performed in the general practice of genomic medicine. Written informed consent was obtained from the proband and family members for prospective information acquisition and academic publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no conflicts of interest associated with this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"48"}}