ArticleGenome medicine2023
Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Can automated copy number variation pathogenicity prediction tools replace manual review under the ACMG framework? A clinical validation.Global medical genetics · 2026Article
- CNV-Hub: an integrated web-based platform for CNV classification and interpretation using multi-algorithm consensus.NAR genomics and bioinformatics · 2026Article
- Article
- Application and clinical utility assessment of natural language processing-based software for copy-number variants interpretation.Journal of translational medicine · 2025Article
- Article
- The evolution of cell-free fetal DNA testing: expanded non-invasive prenatal testing and its effect on target populations.Frontiers in medicine · 2025Article
- Reclassification of Variants Following Renal Genetics Testing: Uncommon Yet Impactful for Diagnosis and Management.Kidney international reports · 2024Article
- Genetic Alterations in a Large Population of Italian Patients Affected by Neurodevelopmental Disorders.Genes · 2024Article
- Exome sequencing improves the molecular diagnostics of paediatric unexplained neurodevelopmental disorders.Orphanet journal of rare diseases · 2024Article
- Variant reclassification and recontact research: A scoping review.Genetics in medicine open · 2024Article
- Clinically Relevant Genetic Considerations for Patients With Tetralogy of Fallot.CJC pediatric and congenital heart disease · 2023Review
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12 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundArray-CGH is the first-tier genetic test both in pre- and postnatal developmental disorders worldwide. Variants of uncertain significance (VUS) represent around 10~15% of reported copy number variants (CNVs). Even though VUS reanalysis has become usual in practice, no long-term study regarding CNV reinterpretation has been reported.
methodsThis retrospective study examined 1641 CGH arrays performed over 8 years (2010-2017) to demonstrate the contribution of periodically re-analyzing CNVs of uncertain significance. CNVs were classified using AnnotSV on the one hand and manually curated on the other hand. The classification was based on the 2020 American College of Medical Genetics (ACMG) criteria.
resultsOf the 1641 array-CGH analyzed, 259 (15.7%) showed at least one CNV initially reported as of uncertain significance. After reinterpretation, 106 of the 259 patients (40.9%) changed categories, and 12 of 259 (4.6%) had a VUS reclassified to likely pathogenic or pathogenic. Six were predisposing factors for neurodevelopmental disorder/autism spectrum disorder (ASD). CNV type (gain or loss) does not seem to impact the reclassification rate, unlike the length of the CNV: 75% of CNVs downgraded to benign or likely benign are less than 500 kb in size.
conclusionsThis study's high rate of reinterpretation suggests that CNV interpretation has rapidly evolved since 2010, thanks to the continuous enrichment of available databases. The reinterpreted CNV explained the phenotype for ten patients, leading to optimal genetic counseling. These findings suggest that CNVs should be reinterpreted at least every 2 years.
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