3.10.26. Variant Site ACMG Classifier

This algorithm computes classifications for each variant based on the ACMG guidelines. These classifications are based on evidence such as population frequencies, conservation scores, splice site algorithms, and functional predictions. The 28 criteria described by the ACMG guidelines are used as the basis for classification and the recommended criteria for each variant is presented alongside the classification. A classification is created for each alternate allele, if there are multiple alleles at the same site the classifications are combined into a list.

Requirements

None

Options

This algorithm allows the user to specify the following options:

  • Internal Database of Classified Variant: Assessment catalog in which to store variant classifications.

  • Gene Thresholds: Used to specify thresholds for various allele number and frequency-based criteria such as BA1, BS1, and PM2.

  • Consortium Sources: These sources contain previously classified variants and are used to determine if a variant has been previously classified as pathogenic or benign.

  • Previously Interpreted Variant Sources: These sources contain expert curated variant interpretations along with classifications, applicable criteria, and associated comments. Variant’s in these sources will be automatically classified and assigned criteria based on the associated interpretation in the source database.

  • Frequency Sources: These sources provide the variant-level allele frequencies used for recommending the criteria BA1, BS1, and PM2. If these sources include sub-population fields, then the sub-population with the largest allele frequency meeting the minimum allele count will be used for the recommendation of criteria.

  • Control Sources: These sources are assumed to contain only healthy adult individuals and are used to recommend the BS2 criterion.

Output

  • Ref/Alt: The Ref/Alt of the evaluated variant.

  • Gene Name: Name of the gene that the transcript is from.

  • Entrez Gene ID: Entrez (RefSeq) Gene ID of the gene.

  • Gene Inheritance: The inheritance model used for the gene.

  • Transcript Name: Transcript Name Field.

  • Transcript Strand: Transcript strand.

  • HGVS cDot: Coding position for scored variant.

  • HGVS pDot: Protein position for scored variant.

  • Sequence Ontology: The predicted interaction between the variant and transcript.

  • Other Transcript Effects: The effects this variant has on alternate transcripts from the same gene.

  • ACMG Classification Criteria: The ACMG classification criteria for each sample.

  • ACMG Classification Criteria Description: The reason each criteria for each ACMG classification was given to each sample.

  • Classification: Variant classification for the given sample, with consideration for previous classifications.

  • Auto Classification: Variant classification for the given sample, without consideration of previous classifications.

  • Previous Classification Count: Number of previous classifications.

  • Previous Classification: The previous classification for the variant.

  • Last Classification Date: Date of most recent classification for the variant.

  • Last Classification Date Unix: Date of most recent classification for the variant in Unix time.

  • Max Sub Population Freq Group Name: The name of the group with the highest reported frequency.

  • Max Allele Frequency: The allele frequency of the group with the highest reported frequency.

  • Max Allele Number: The total number of alleles in the group with the highest reported frequency.

  • Max Allele Count: The number of times this allele was found in the group with the highest reported frequency.