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We developed a rules-based scoring system to classify DNA variants into five categories including pathogenic, likely pathogenic, variant of uncertain significance (VUS), likely benign, and benign. Over 16,500 pathogenicity assessments on 11,894 variants from 338 genes were analyzed for pathogenicity based on prediction tools, population frequency, co-occurrence, segregation, and functional studies collected from internal and external sources. Scores were calculated by trained scientists using a quantitative framework that assigned differential weighting to these five types of data. We performed descriptive and comparative statistics on the dataset and tested interobserver concordance among the trained scientists. Private variants defined as variants found within single families (n = 5,182), were either VUS (80.5%; n = 4,169) or likely pathogenic (19.5%; n = 1,013). The remaining variants (n = 6,712) were VUS (38.4%; n = 2,577) or likely benign/benign (34.7%; n = 2,327) or likely pathogenic/pathogenic (26.9%, n = 1,808). Exact agreement between the trained scientists on the final variant score was 98.5% [95% confidence interval (CI) (98.0, 98.9)] with an interobserver consistency of 97% [95% CI (91.5, 99.4)]. Variant scores were stable and showed increasing odds of being in agreement with new data when re-evaluated periodically. This carefully curated, standardized variant pathogenicity scoring system provides reliable pathogenicity scores for DNA variants encountered in a clinical laboratory setting.
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http://dx.doi.org/10.1002/humu.22918 | DOI Listing |
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December 2024
Department of General Surgery, Istanbul Training and Research Hospital, Istanbul, Turkey.
Background: Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies among different subtypes of breast cancer.
View Article and Find Full Text PDFVet Anim Sci
March 2025
International Center for Agricultural Research in the Dry Areas (ICARDA), P.O. Box 5689, Addis Ababa, Ethiopia.
This study assessed the supplemental effect of flushing Menz breeding rams with local agro-industrial by-products on their reproductive performance and semen quality. In a completely randomized design, rams ( 49) with an initial weight of 25.69+2.
View Article and Find Full Text PDFBased on theoretical premises of ecological systems theory and the compensatory hypothesis, a subset of data from the Family Life Project ( = 773), a population-based study of rural families with low incomes, were used to test for associations between maternal literacy in infancy and children's academic outcomes and teacher-reported problem behaviors in kindergarten. A second aim tested whether increased time in child care averaged from 6-36 months moderated such relations. Results indicated that maternal literacy was significantly positively related to academic outcomes ( = .
View Article and Find Full Text PDFPhys Imaging Radiat Oncol
October 2024
Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Radiation Oncology, De Boelelaan 1117, Amsterdam, the Netherlands.
Background And Purpose: Segmentation imperfections (noise) in radiotherapy organ-at-risk segmentation naturally arise from specialist experience and image quality. Using clinical contours can result in sub-optimal convolutional neural network (CNN) training and performance, but manual curation is costly. We address the impact of simulated and clinical segmentation noise on CNN parotid gland (PG) segmentation performance and provide proof-of-concept for an easily implemented auto-curation countermeasure.
View Article and Find Full Text PDFDermatol Res Pract
December 2024
Department of Clinical Sciences, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan.
Rosacea, a chronic facial dermatosis, poses a substantial global prevalence burden. Its impact extends beyond physical symptoms, affecting patient quality of life, self-esteem, and psychosocial functioning. This study aims to assess the health-related quality of life and emotional well-being in Jordanian rosacea patients in comparison to healthy controls.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!