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

"We are very grateful for the work you do with Alamut and continuing to improve it. We use it on daily basis to help us interpret variants for clinical tests including our technicians, analysts, genetic counselors and lab directors. Alamut has the comprehensive information available for interpreting variants and great documentation. I’ve recommended Alamut to many customers who ask me about the tools that I use. Many thanks to you for making this possible."

AMMAR HUSAMI
Cincinnati Children's Hospital Medical Center

イベント

17.10.2017

ASHG 2017

USA

27.05.2017

ESHG 2017

デンマーク