Interactive Biosoftware

ACMG Guidelines

ACMG/AMP Variant Interpretation Standards and Guidelines Support in Alamut® Visual and Alamut® Batch

The 2015 report from the American College of Medical Genetics and Genomics (ACMG) provides updated recommendations for the reporting and interpretation of sequence variants for Mendelian disorders in a clinical context (Richards et al., 2015. Genet Med 17:405–424).
The table below summarizes ACMG recommendations and suggested resources supported or implemented in Alamut® Visual and Alamut® Batch.

Terminology
  • Term “variant” (sometimes also “variation”) used throughout the software, not “mutation” nor “polymorphism” (as of upcoming v.2.8.0)
  • ACMG variant classification terminology (pathogenic, likely pathogenic, uncertain significance, likely benign and benign) is the default variant description scheme
Nomenclature
  • HGVS variant nomenclature v2.0 (15.11 as of May 1st 2016) compliance
  • Variant reports include sequence references (RefSeq, LRG)
  • Coding nomenclature described using the “A” for ATG translation initiation codon as position 1
  • Use of genomic coordinates, defined according to standard genome builds (GRCh37, GRCh38) or genomic reference sequences (RefSeqGenes, LRGs)
  • All clinically relevant transcripts including alternate transcripts available
  • Reference transcripts automatically suggested (longest known) or selected by user
  • Supported exceptions to the HGVS nomenclature: "X" can be used instead of “*” in nonsense variants; Exons can be numbered according to specific schemes
Literature mining
  • Automated queries to NCBI PubMed and Google
DatabasesPopulation databases
  • Exome Aggregation Consortium (ExAC)
  • Exome Variant Server (EVS)
  • dbSNP
  • 1000 Genomes: SNVs and short indels (through dbSNP)
  • Other population databases: Genome of the Netherlands (GoNL), Japan Human Genetic Variation Database (HGVD), 2,000 Danes WES (Diabetes Type 2 Study)

Disease databases
  • ClinVar
  • OMIM
  • HGMD® Professional
  • Locus/Disease/Ethnic/Other-Specific Databases: Semi-automated access to LOVDs; Quick access to HGVS-listed databases

Sequence databases
  • NCBI Genome (Genome Reference Consortium)
  • NCBI RefSeq
  • Locus Reference Genomic and Locus Reference Genomic (LRG)
  • MitoMap (rCRS) for the Human Mitochondrial DNA
  • Ensembl

Internal variant and sequence annotation database
  • Stored locally
  • HIPAA-compliant
Computational (in silico) predictive programsMissense
  • Align GVGD
  • SIFT
  • MutationTaster

Splicing
  • GeneSplicer
  • Human Splicing Finder
  • MaxEntScan
  • NNSplice
  • SpliceSiteFinder

Nucleotide conservation
  • PhastCons
  • PhyloP


Alamut Visualに
寄せられた感想

"Alamut is the best tool I have used for the annotation of DNA variants. It has a great user interface, combines data from multiple sources and allows for ease of variant interpretation by clinical geneticists."

JORDAN LERNER-ELLIS, Ph.D.
Mt. Sinai Hospital, Toronto

イベント

22.03.2017

ACMG 2017

USA

31.10.2016

Variant Effect Prediction Training Course

Greece