ArticleBMC bioinformatics2018
Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase.
Article in BMC bioinformatics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 31 citations in OpenAlex.
- A Maternal Loss-of-Function Variant in KHDC3L Gene Causes a Range of Adverse Pregnancy Outcomes: A Case Report.Molecular genetics & genomic medicine · 2025Article
- Safety and Tolerability of a Shorter Agalsidase Beta Infusion Time in Patients with Classic or Later-Onset Fabry Disease.Biomedicines · 2024Article
- Enhancing Missense Variant Pathogenicity Prediction with MissenseNet: Integrating Structural Insights and ShuffleNet-Based Deep Learning Techniques.Biomolecules · 2024Article
- Congenital disorders of glycosylation: narration of a story through its patents.Orphanet journal of rare diseases · 2023Review
- Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances.Clinical epigenetics · 2022Article
- Challenging the traditional approach for interpreting genetic variants: Lessons from Fabry disease.Clinical genetics · 2022Review
- Protective Role of aGenes · 2021Article
- Loss-of-function maternal-effect mutations of PADI6 are associated with familial and sporadic Beckwith-Wiedemann syndrome with multi-locus imprinting disturbance.Clinical epigenetics · 2020Article
- Assessing Lysosomal Disorders in the NGS Era: Identification of Novel Rare Variants.International journal of molecular sciences · 2020Article
- GLA missense and promoter variants co-segregating in a Chinese family with Fabry disease.Annals of translational medicine · 2020Article
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6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeverity gradation of missense mutations is a big challenge for exome annotation. Predictors of deleteriousness that are most frequently used to filter variants found by next generation sequencing, produce qualitative predictions, but also numerical scores. It has never been tested if these scores correlate with disease severity.
resultswANNOVAR, a popular tool that can generate several different types of deleteriousness-prediction scores, was tested on Fabry disease. This pathology, which is caused by a deficit of lysosomal alpha-galactosidase, has a very large genotypic and phenotypic spectrum and offers the possibility of associating a quantitative measure of the damage caused by mutations to the functioning of the enzyme in the cells. Some predictors, and in particular VEST3 and PolyPhen2 provide scores that correlate with the severity of lysosomal alpha-galactosidase mutations in a statistically significant way.
conclusionsSorting disease mutations by severity is possible and offers advantages over binary classification. Dataset for testing and training in silico predictors can be obtained by transient transfection and evaluation of residual activity of mutants in cell extracts. This approach consents to quantitative data for severe, mild and non pathological variants.
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