ArticleCurrent genomics2020
The Experimentally Obtained Functional Impact Assessments of 5' Splice Site GT'GC Variants Differ Markedly from Those Predicted.
Article in Current genomics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- When splicing is not all or none: GT>GC 5' splice-site variants as a model for intermediate effects and challenges in variant classification.HGG advances · 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
- A Plot Twist: When RNA Yields Unexpected Findings in Paired DNA-RNA Germline Genetic Testing.Genes · 2025Article
- SPINK1-related chronic pancreatitis: A model that encapsulates the spectrum of variant effects, genetic complexity, and classificatory challenges.American journal of human genetics · 2025Article
- The novel c.1227+2T>C variant in RHD results in the serological D-negative phenotype.Transfusion · 2025Article
- Genetics and clinical implications of SPINK1 in the pancreatitis continuum and pancreatic cancer.Human genomics · 2025Review
- Alu insertion-mediated dsRNA structure formation with pre-existing Alu elements as a disease-causing mechanism.American journal of human genetics · 2024Article
- Identification and analysis of short indels inducing exon extension/shrinkage events.FEBS open bio · 2024Article
- Combining full-length gene assay and SpliceAI to interpret the splicing impact of all possible SPINK1 coding variants.Human genomics · 2024Article
- Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup.American journal of human genetics · 2023Article
- APPLICATION OF THE ACMG/AMP FRAMEWORK TO CAPTURE EVIDENCE RELEVANT TO PREDICTED AND OBSERVED IMPACT ON SPLICING: RECOMMENDATIONS FROM THE CLINGEN SVI SPLICING SUBGROUP.medRxiv : the preprint server for health sciences · 2023Article
- Case report: A novelFrontiers in neurology · 2023Article
- Combining genetic constraint with predictions of alternative splicing to prioritize deleterious splicing in rare disease studies.BMC bioinformatics · 2022Article
- Article
- High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency.American journal of human genetics · 2021Article
- Splicing Outcomes of 5' Splice Site GT>GC Variants That Generate Wild-Type Transcripts Differ Significantly Between Full-Length and Minigene Splicing Assays.Frontiers in genetics · 2021Article
- Splicing in the Diagnosis of Rare Disease: Advances and Challenges.Frontiers in genetics · 2021Review
- Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introduction5' splice site GT>GC or +2T>C variants have been frequently reported to cause human genetic disease and are routinely scored as pathogenic splicing mutations. However, we have recently demonstrated that such variants in human disease genes may not invariably be pathogenic. Moreover, we found that no splicing prediction tools appear to be capable of reliably distinguishing those +2T>C variants that generate wild-type transcripts from those that do not. METHODOLOGY: Herein, we evaluated the performance of a novel deep learning-based tool, SpliceAI, in the context of three datasets of +2T>C variants, all of which had been characterized functionally in terms of their impact on pre-mRNA splicing. The first two datasets refer to our recently described "
resultsComparison of the SpliceAI-predicted and experimentally obtained functional impact assessments of these variants (and smaller datasets of +2T>A and +2T>G variants) revealed that although SpliceAI performed rather better than other prediction tools, it was still far from perfect. A key issue was that the impact of those +2T>C (and +2T>A) variants that generated wild-type transcripts represents a quantitative change that can vary from barely detectable to an almost full expression of wild-type transcripts, with wild-type transcripts often co-existing with aberrantly spliced transcripts.
conclusionOur findings highlight the challenges that we still face in attempting to accurately identify splice-altering variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.