ArticleHuman mutation2015
Functional classification of BRCA2 DNA variants by splicing assays in a large minigene with 9 exons.
Article in Human mutation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 53 citations in OpenAlex.
- Minigene-based characterization and classification of splice-associated variants in succinate dehydrogenase B.NPJ precision oncology · 2026Article
- Generation of functional noncanonical donor splice sites by +2T variants in breast cancer susceptibility genes: impact on clinical interpretation.The Journal of pathology · 2026Article
- Experimental Mis-Splicing Assessment and ACMG/AMP-Guided Classification of 47International journal of molecular sciences · 2026Article
- Unproductive alternative splicing of ATM exon 7: mapping of critical regulatory elements and identification of 34 spliceogenic variants.Journal of molecular medicine (Berlin, Germany) · 2025Article
- The SeqSplice multiplexed minigene splicing assay for characterization and quantitation of variant-inducedGenome research · 2025Article
- Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays.Human genomics · 2025Article
- Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing.NPJ precision oncology · 2024Article
- Splicing Dysregulation of Non-Canonical GC-5' Splice Sites of Breast Cancer Susceptibility GenesCancers · 2024Article
- Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model.Journal of human genetics · 2023Article
- Minigene Splicing Assays and Long-Read Sequencing to Unravel Pathogenic Deep-Intronic Variants inInternational journal of molecular sciences · 2023Article
- Splicing Analysis of 16Cancers · 2022Article
- Minigene-based splicing analysis and ACMG/AMP-based tentative classification of 56 ATM variants.The Journal of pathology · 2022Article
- Actionable secondary findings following exome sequencing of 836 non-obstructive azoospermia cases and their value in patient management.Human reproduction (Oxford, England) · 2022Article
- Minigene Splicing Assays Identify 20 Spliceogenic Variants of the Breast/Ovarian Cancer Susceptibility GeneCancers · 2022Article
- Splicing predictions, minigene analyses, and ACMG-AMP clinical classification of 42 germline PALB2 splice-site variants.The Journal of pathology · 2022Article
- Germline Variants ofCancers · 2022Article
- Article
- Comprehensive Functional Characterization and Clinical Interpretation of 20 Splice-Site Variants of theCancers · 2020Article
- Reclassification ofJournal of gynecologic oncology · 2020Article
- Pathogenic evaluation of synonymous COL4A5 variants in X-linked Alport syndrome using a minigene assay.Molecular genetics & genomic medicine · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous pathogenic DNA variants impair the splicing mechanism in human genetic diseases. Minigenes are optimal approaches to test variants under the splicing viewpoint without the need of patient samples. We aimed to design a robust minigene construct of the breast cancer gene BRCA2 in order to investigate the impact of variants on splicing. BRCA2 exons 19-27 (MGBR2_ex19-27) were cloned in the new vector pSAD. It produced a large transcript of the expected size (2,174 nucleotides) and exon structure (V1-ex19-27-V2). Splicing assays showed that 18 (17 splice-site and 1 silencer variants) out of 40 candidate DNA variants induced aberrant patterns. Twenty-four anomalous transcripts were accurately detected by fluorescent-RT-PCR that were generated by exon-skipping, alternative site usage, and intron-retention events. Fourteen variants induced major anomalies and were predicted to disrupt protein function so they could be classified as pathogenic. Furthermore, minigene mimicked previously reported patient RNA outcomes of seven variants supporting the reproducibility of minigene assays. Therefore, a relevant fraction of variants are involved in breast cancer through splicing alterations. MGBR2_ex19-27 is the largest reported BRCA2 minigene and constitutes a valuable tool for the functional and clinical classification of sequence variations.
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