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

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]