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This study presents the clinical and genetic findings of a Danish CVID cohort and investigate whether initial genetic findings can be re-classified upon re-evaluation years later in time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>From 2016 to 2021, individuals with CVID or a CVID-like-phenotype were examined using whole exome or whole genome sequencing in combination with comprehensive gene-panels. The results were re-evaluated to ensure up-to-date American College of Medical Genetics and Genomics (ACMG) classification after a median of 3.9 years. Further, a clinical-interpretation-algorithm is proposed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 69 enrolled individuals, 57 met the current ESID-CVID-criteria of whom 29 (51%) had a genetic find. In total 67 ACMG class 3 to 5 variants were detected in 39 different genes. Class 3 variants (variants of uncertain significance (VUS)) accounted for 81% in the initial analysis. Upon re-evaluation 17 of 54 (31%) of the originally reported VUS were re-classified to a different ACMG-class or excluded. The developed clinical-interpretation-algorithm demonstrated high interobserver-agreement. A \u201cdefinite\/probable\u201d disease causing (or contributing) genetic variant was found in 19% of the CVID-cohort and a \u201cpossible\u201d in 18%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A genetic cause of CVID could be identified in a minority of CVID-individuals, whereas the majority had no or uncertain genetic findings. Re-evaluation of genetic results over time is recommended, though VUS remain a significant challenge in CVID-genetics. Therefore, continued research in both CVID-genetics and in non-genetic causes of CVID is needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10875-025-01896-w","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T23:09:25Z","timestamp":1748819365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetics in a Danish Common Variable Immunodeficiency Cohort"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9053-9047","authenticated-orcid":false,"given":"Camilla Heldbjerg","family":"Drabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3223-0440","authenticated-orcid":false,"given":"Mira Marie","family":"Laustsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9740-6522","authenticated-orcid":false,"given":"Hanne Vibeke","family":"Marquart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4886-0419","authenticated-orcid":false,"given":"Hans Jakob","family":"Hartling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5267-3173","authenticated-orcid":false,"given":"Rasmus L.","family":"Marvig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-0144","authenticated-orcid":false,"given":"Jannik","family":"Helweg-Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4228-3822","authenticated-orcid":false,"given":"Ann-Brit Eg","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-7850","authenticated-orcid":false,"given":"Jens","family":"Lundgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2370-1657","authenticated-orcid":false,"given":"Marie","family":"Helleberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1719-9856","authenticated-orcid":false,"given":"Line","family":"Borgwardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-500X","authenticated-orcid":false,"given":"Terese L.","family":"Katzenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"1896_CR1","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1007\/s10875-022-01352-z","volume":"42","author":"A Bousfiha","year":"2022","unstructured":"Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, et al. 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