| http://purl.uniprot.org/citations/33609447 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33609447 | http://www.w3.org/2000/01/rdf-schema#comment | "Determination of the clinical relevance of rare germline variants of uncertain significance (VUSs) in the BRCA2 cancer predisposition gene remains a challenge as a result of limited availability of data for use in classification models. However, laboratory-based functional data derived from validated functional assays of known sensitivity and specificity may influence the interpretation of VUSs. We evaluated 252 missense VUSs from the BRCA2 DNA-binding domain by using a homology-directed DNA repair (HDR) assay and identified 90 as non-functional and 162 as functional. The functional assay results were integrated with other available data sources into an ACMG/AMP rules-based classification framework used by a hereditary cancer testing laboratory. Of the 186 missense variants observed by the testing laboratory, 154 were classified as VUSs without functional data. However, after applying protein functional data, 86% (132/154) of the VUSs were reclassified as either likely pathogenic/pathogenic (39/132) or likely benign/benign (93/132), which impacted testing results for 1,900 individuals. These results indicate that validated functional assay data can have a substantial impact on VUS classification and associated clinical management for many individuals with inherited alterations in BRCA2."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajhg.2021.02.005"xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Lee K.Y."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Hu C."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Goldgar D.E."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Richardson M.E."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Chao E."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Gnanaolivu R."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Couch F.J."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Monteiro A.N.A."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Hart S.N."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Pesaran T."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Polley E.C."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "LaDuca H."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Fulk K."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Deckman A.M."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/author | "Durda K.M."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/name | "Am J Hum Genet"xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/pages | "458-468"xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/title | "Strong functional data for pathogenicity or neutrality classify BRCA2 DNA-binding-domain variants of uncertain significance."xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://purl.uniprot.org/core/volume | "108"xsd:string |
| http://purl.uniprot.org/citations/33609447 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/33609447 |
| http://purl.uniprot.org/citations/33609447 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/33609447 |