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


Qué es lo que ellos dicen
acerca de Alamut Visual

"We were early Alamut adopters and this software has become essential to our daily diagnosis lab practice, saving time and reducing mistakes. The intuitivity of use and the new functionalities are a very useful help in our daily work."

PASCALE RICHARD M.D. Ph.D.
Paris, France

Eventos

22.03.2017

ACMG 2017

Estados Unidos

31.10.2016

Variant Effect Prediction Training Course

Grecia