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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 [88]
ENCODE Annotation of potential functional elements (for example, histone tail modifications) in several cell lines [89]
Epigenomics Roadmap Annotation of potential functional elements (for example, DNAse I hypersensitive sites) in many human tissues and primary cells [90]
FANTOM5 Annotation of transcriptional enhancers in many human tissues and primary cells through detection of bidirectional capped transcription [91]
GERP Identifies constrained elements in multiple alignments by quantifying substitution deficits [92]
HaploReg Visualization of DNA polymorphisms along with their predicted chromatin state, their sequence conservation across mammals, and their effect on regulatory motifs [93]
Phen-Gen Method that combines patients' disease symptoms and sequencing data with prior domain knowledge to identify the causative genes for rare disorders [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 [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 [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 [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 [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. [99]
  1. CNV, copy number variant; SNP, single nucleotide polymorphism.