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Table 2 Partial list of tools and resources to annotate DNA sequence variants

From: Rare variant association studies: considerations, challenges and opportunities

Tool/resource Description URL Reference
CADD A framework that integrates multiple annotations into one metric by contrasting variants that survived natural selection with simulated mutations http://cadd.gs.washington.edu/ [88]
ENCODE Annotation of potential functional elements (for example, histone tail modifications) in several cell lines https://www.encodeproject.org/ [89]
Epigenomics Roadmap Annotation of potential functional elements (for example, DNAse I hypersensitive sites) in many human tissues and primary cells http://www.roadmapepigenomics.org/ [90]
FANTOM5 Annotation of transcriptional enhancers in many human tissues and primary cells through detection of bidirectional capped transcription http://enhancer.binf.ku.dk/ [91]
GERP Identifies constrained elements in multiple alignments by quantifying substitution deficits http://mendel.stanford.edu/SidowLab/downloads/gerp/ [92]
HaploReg Visualization of DNA polymorphisms along with their predicted chromatin state, their sequence conservation across mammals, and their effect on regulatory motifs http://www.broadinstitute.org/mammals/haploreg/haploreg.php [93]
Phen-Gen Method that combines patients' disease symptoms and sequencing data with prior domain knowledge to identify the causative genes for rare disorders http://phen-gen.org/about.html [94]
PolyPhen-2 A tool that predicts the possible impact of an amino acid substitution on the structure and function of a human protein using straightforward physical and comparative considerations http://genetics.bwh.harvard.edu/pph2/ [95]
RegulomeDB A database that annotates SNPs with known and predicted regulatory elements in the intergenic regions of the human genome using gene expression, ENCODE and literature-mining data http://regulomedb.org/ [96]
RVIS This score is designed to rank genes in terms of whether they have more or less common functional genetic variation relative to the genome-wide expectation given the amount of apparently neutral variation the gene has http://chgv.org/GenicIntolerance/ [97]
SIFT Predicts whether an amino acid substitution affects protein function based on the degree of conservation of amino acid residues in sequence alignments derived from closely related sequences http://sift.jcvi.org/ [98]
VEP Determines the effect of your variants (SNPs, insertions, deletions, CNVs or structural variants) on genes, transcripts and protein sequence, as well as regulatory regions. http://useast.ensembl.org/info/docs/tools/vep/index.html?redirect=no [99]
  1. CNV, copy number variant; SNP, single nucleotide polymorphism.