ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data

Wang, Kai; Li, Mingyao; Hákonarson, Hákon

doi:10.1093/nar/gkq603

Cited by 11,998 publications

(9,547 citation statements)

References 21 publications

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“…Targeted gene variants were called by the Unified Genotyper in GATK and also were recalibrated by GATK based on dbSNP137, Mills indels, HapMap, and Omni. Finally, we used ANNOVAR 15 to annotate the variants.…”

Section: Detection Of Single-nucleotide Variants and Insertion/ Deletmentioning

confidence: 99%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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Purpose: This study was designed to delineate genetic contributions, if any, to sporadic forms of mild to moderate sensorineural hearing loss (SNHL) not related to GJB2 mutations (DFNB1) in a pediatric population. Methods:We recruited 11 non-DFNB1 simplex cases of mild to moderate SNHL in children. We applied whole-exome sequencing to all 11 probands. We used a filtering strategy assuming that de novo variants of known autosomal dominant (AD) deafness genes, biallelic mutations in autosomal recessive (AR) genes, monoallelic mutations in X chromosome genes for males, and digenic inheritance could be associated. Candidate variants first were prioritized with allele frequency in public databases and confirmed by a phase or a segregation test in each family. Additional information from the literature or public databases was used to identify strong candidate variants.Results: Strong candidate variants were detected in 5 of 11 probands (45.4%). A diverse mode of inheritance implicated the sporadic occurrence of the phenotype. AR mutations in OTOGL and SERPINB6 and digenic inheritance involving two deafness genes, GPR98 and PDZ7, were detected. A de novo AD mutation also was detected in TECTA and MYH14. No syndromic feature was detected in individuals with GPR98/PDZ7 or MYH14 variants in our cohort at this moment. Conclusion:Mild to moderate pediatric SNHL, even if sporadic, features a strong genetic etiology and can manifest via diverse modes of inheritance. In addition, a multidisciplinary approach should be used for a correct diagnosis. Genet Med advance online publication 26 February 2015

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Section: Detection Of Single-nucleotide Variants and Insertion/ Deletmentioning

confidence: 99%

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Kim

Park

et al. 2015

Genetics in Medicine

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“…The reads were mapped to the hg19 human reference using Burrows‐Wheeler Aligner (BWA) 0.6.2‐r12615 and single‐nucleotide variants (SNVs), and insertions and/or deletions (indels) were called using the Genome Analysis Toolkit (GATK) v. 1.6–13 16. After quality filtering steps, variants were annotated using ANNOVAR 17. We prioritized the variants identified in enrolled CP patients as described below (Fig.…”

Section: Methodsmentioning

confidence: 99%

Genomic analysis identifies masqueraders of full‐term cerebral palsy

Takezawa

Kikuchi

Haginoya

et al. 2018

Ann Clin Transl Neurol

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ObjectiveCerebral palsy is a common, heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent studies have suggested genetic diseases can be misdiagnosed as cerebral palsy. We hypothesized that two simple criteria, that is, full‐term births and nonspecific brain MRI findings, are keys to extracting masqueraders among cerebral palsy cases due to the following: (1) preterm infants are susceptible to multiple environmental factors and therefore demonstrate an increased risk of cerebral palsy and (2) brain MRI assessment is essential for excluding environmental causes and other particular disorders.MethodsA total of 107 patients—all full‐term births—without specific findings on brain MRI were identified among 897 patients diagnosed with cerebral palsy who were followed at our center. DNA samples were available for 17 of the 107 cases for trio whole‐exome sequencing and array comparative genomic hybridization. We prioritized variants in genes known to be relevant in neurodevelopmental diseases and evaluated their pathogenicity according to the American College of Medical Genetics guidelines.ResultsPathogenic/likely pathogenic candidate variants were identified in 9 of 17 cases (52.9%) within eight genes: CTNNB1,CYP2U1,SPAST,GNAO1,CACNA1A,AMPD2,STXBP1, and SCN2A. Five identified variants had previously been reported. No pathogenic copy number variations were identified. The AMPD2 missense variant and the splice‐site variants in CTNNB1 and AMPD2 were validated by in vitro functional experiments.InterpretationThe high rate of detecting causative genetic variants (52.9%) suggests that patients diagnosed with cerebral palsy in full‐term births without specific MRI findings may include genetic diseases masquerading as cerebral palsy.

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“…Variants were called using three programs: MuTect (SNPs),13 SomaticSniper (SNPs),14 and Strelka (INDELs) 15. Variants were annotated using AnnoVar for functional changes (nonsynonymous mutations) to RefSeq gene annotation 16. For this analysis, mutation detection was restricted to variants identified within coding exons, excluding all noncoding exons and UTRs.…”

Section: Methodsmentioning

confidence: 99%

Mutation analysis of adenomas and carcinomas of the colon: Early and late drivers

Wolff

Hoffman

Wolff

et al. 2018

Genes Chromosomes & Cancer

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Colorectal cancer (CRC) accounts for about 8% of all new cancer cases diagnosed in the US. We used whole exome sequence data from triplet samples (colon carcinoma, colon adenoma, and normal tissue) from 18 individuals to assess gene mutation rates. Of the 2 204 genes that were mutated, APC, TTN, TP53, KRAS, OBSCN, SOX9, PCDH17, SIGLEC10, MYH6, and BRD9 were consistent with genes being an early driver of carcinogenesis, in that they were mutated in multiple adenomas and multiple carcinomas. Fifty‐two genes were mutated in ≥12.5% of microsatellite stable (MSS) carcinomas but not in any of the adenomas, in line with the profile of a late driver event involved in tumor progression. Thirty‐eight genes were sequenced in a larger independent set of 148 carcinoma/normal tissue pairs to obtain more precise mutation frequencies. Eight of the genes, APC, TP53, ATM, CSMD3, LRP1B, RYR2, BIRC6, and MUC17, contained mutations in >20% of the carcinomas. Interestingly, mutations in four genes in addition to APC that are associated with dysregulation of Wnt signaling, were all classified as early driver events. Most of the genes that are commonly associated with colon cancer, including APC, TP53, and KRAS, were all classified as being early driver genes being mutated in both adenomas and carcinomas. Classifying genes as potential early and late driver events points to candidate genes that may help dissect pathways involved in both tumor initiation and progression.

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ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data

Cited by 11,998 publications

References 21 publications

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Whole-exome sequencing reveals diverse modes of inheritance in sporadic mild to moderate sensorineural hearing loss in a pediatric population

Genomic analysis identifies masqueraders of full‐term cerebral palsy

Mutation analysis of adenomas and carcinomas of the colon: Early and late drivers

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