VarAFT: a variant annotation and filtration system for human next generation sequencing data

Desvignes, Jean-Pierre; Bartoli, Marc; Delague, Valérie; Krahn, Martin; Miltgen, Morgane; Béroud, Christophe; Salgado, David

doi:10.1093/nar/gky471

Cited by 158 publications

(111 citation statements)

References 39 publications

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“…The data were analyzed as described elsewhere [18]. Annotation, filtering, and prioritization of variants were carried out using VarAFT software [19]. The results were then filtered under de novo dominance and recessive hypotheses.…”

Section: Whole Exome Sequencing and Molecular Analyses Patientmentioning

confidence: 99%

Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum

Urreizti

López-Martín

Martinez‐Monseny

et al. 2020

Orphanet J Rare Dis

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Background: Pathogenic variants of the lysine acetyltransferase 6A or KAT6A gene are associated with a newly identified neurodevelopmental disorder characterized mainly by intellectual disability of variable severity and speech delay, hypotonia, and heart and eye malformations. Although loss of function (LoF) mutations were initially reported as causing this disorder, missense mutations, to date always involving serine residues, have recently been associated with a form of the disorder without cardiac involvement.Results: In this study we present five new patients, four with truncating mutations and one with a missense change and the only one not presenting with cardiac anomalies. The missense change [p.(Gly359Ser)], also predicted to affect splicing by in silico tools, was functionally tested in the patient's lymphocyte RNA revealing a splicing effect for this allele that would lead to a frameshift and premature truncation.Conclusions: An extensive revision of the clinical features of these five patients revealed high concordance with the 80 cases previously reported, including developmental delay with speech delay, feeding difficulties, hypotonia, a high bulbous nose, and recurrent infections. Other features present in some of these five patients, such as cryptorchidism in males, syndactyly, and trigonocephaly, expand the clinical spectrum of this syndrome.

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Section: Whole Exome Sequencing and Molecular Analyses Patientmentioning

confidence: 99%

Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum

Urreizti

López-Martín

Martinez‐Monseny

et al. 2020

Orphanet J Rare Dis

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“…SNP and Indel variants called using the GATK Unified Genotyper for each sample (DePristo et al, 2011). Variants were called using high stringency settings and annotated with VarAFT software 2.16 (Desvignes et al, 2018) containing information from dbSNP147 and gnomAD v2.11 1 . Variant interpretation was limited to the genes that occurred in the 59 medically actionable genes listed in the ACMG guidelines (Kalia et al, 2017).…”

Section: Wes Analysismentioning

confidence: 99%

Actionable Exomic Secondary Findings in 280 Lebanese Participants

2020

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The expanded use of NGS tests in genetic diagnosis enables the massive generation of data related to each individual, among which some findings are of medical value. Over the last three and a half years, 280 unrelated Lebanese patients, presenting a wide spectrum of genetic disorders were referred to our center for genetic evaluation by WES. Molecular diagnosis was established in 56% of the cases, as was previously reported. The current study evaluates secondary findings in these patients in 59 genes, linked to conditions mostly responsive to medical interventions, as per the ACMG guidelines. Our analysis allowed us to detect 19 pathogenic/likely pathogenic variants in 24 individuals from our cohort. Dominant actionable variants were found in 17 individuals representing 6% of the studied population. Genes associated with dominant cardiac diseases were the most frequently mutated: variants were found in 2.1% of our cohort. Genetic predisposition to cancer syndromes was observed in 1.07% of the cases. In parallel to dominant disease alleles, our analysis identified a recessive pathogenic disease allele in 2.5% of the individuals included in this study. Of interest, some variants were detected in different patients from our cohort thus urging the study of their prevalence in our population and the implementation, when needed, of specific genetic testing in the neonatal screening panel. In conclusion, here we report the first study estimating the actionable pathogenic variant load in the Lebanese population. Communicating current findings to the patients will enable them to benefit from a multi-disciplinary approach. Furthermore, tailoring the ACMG guidelines to the population is suggested, especially in highly consanguineous populations where the information related to recessive alleles might be highly beneficial to patients and their families.

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“…VarAFT [2] was used to obtain exon coverage for these genes. The default options were used to generate the pdf report using CovReport with Show gene transcript and Show statistics options activated.…”

Section: Resultsmentioning

confidence: 99%

“…Given the critical importance of coverage data, several tools have been previously developed to evaluate the coverage of target regions after short-read sequencing in a diagnostic setting [2,6,7].…”

Section: Discussionmentioning

confidence: 99%

A new tool CovReport generates easy-to-understand sequencing coverage summary for diagnostic reports

Gorokhov

Cerino

Bartoli

et al. 2019

Preprint

Self Cite

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In order to properly interpret the results of a diagnostic gene panel sequencing test, gene coverage needs to be taken into consideration. If coverage is too low, an additional re-sequencing test is needed to make sure that a pathogenic variant is not missed. To facilitate the interpretation of coverage data, we designed CovReport, a novel easy-to-use visualization tool. CovReport generates a concise coverage summary that allows one-glance assessment of the sequencing test performance. Both gene-level and exon-level coverage can be immediately appreciated and taken into consideration for further medical decisions. CovReport does not require complex installation and can thus be easily implemented in any diagnostic laboratory setting. A user-friendly interface generates a graphic summary of coverage that can be directly included in the diagnostic report. In addition to a stand-alone version, we also provide a command line version of CovReport that can be integrated into any bioinformatics pipeline. This flexible tool is now part of routine sequencing analysis at the Department of Medical Genetics at La Timone Hospital (Marseille, France). Availability and implementation: CovReport is available at http://jdotsoft.com/CovReport.php. It is implemented in Java and supported on Windows, Mac OS X and Linux.

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VarAFT: a variant annotation and filtration system for human next generation sequencing data

Cited by 158 publications

References 39 publications

Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum

Five new cases of syndromic intellectual disability due to KAT6A mutations: widening the molecular and clinical spectrum

Actionable Exomic Secondary Findings in 280 Lebanese Participants

A new tool CovReport generates easy-to-understand sequencing coverage summary for diagnostic reports

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