Understanding a Flex Family Report

Jeanette McCarthy -

Flex (no longer available) was a preconfigured workflow to analyze of family data based on mode of inheritance, and cohorts based on shared variants or genes. Flex reports may have previously been generated in your workspace.  Although it is no longer possible to launch a new Flex workflow, those reports previously generated can still be seen.  Just click on the Flex Trio or Flex Quad report link. 

The following table explains the columns that appear on the report. 

Flex Family Report Headers

Review Priority A visual prioritization of variants based on three data elements: ClinVar, Allele Frequency and Effect. See Appendix 3 for more details.

Reports generated from Opal Pipeline 4.3 and below data use the Variant Classification (previously Predicted Class) field. See Appendix 7 for more details.

Gene HGNC symbol of the gene.
Position Chromosome and base pair position.
Change Reference position and alleles reported in the sample genome. In addition, the HGVS notation for the nucleotide and protein change (if any) for a representative transcript.
dbSNP dbSNP identifier if one exists (and an embedded URL link to dbSNP).
Zygosity Genotype of the variant of the proband (homozygote or heterozygote).
Sibling Zygosity Genotype of the variant in the affected or unaffected sibling (Optional).
Father Zygosity Genotype of the variant of the father.
Mother Zygosity Genotype of the variant of the mother.
Effect Impact of the variant on the gene and transcripts; i.e. synonymous, non-synonymous, stop gain/loss, indel/frameshift, and splice variants.
Frequencies from 1000 Genomes Project, Exome Variant Server and ExAC. Click on the hyperlinks to access the ethnic subpopulation frequencies.
Omicia score Proprietary impact assessment score that provides a rational aggregation of other variant scoring algorithms. Values range from 0 t0 1, the greater the value the more likely that a variant is deleterious or is located in a highly conserved region (see Appendix 2).
VVP Score The VAAST Variant Prioritization score applies the VAAST algorithm at the variant level. VAAST takes predicted protein impact, conservation and allele frequency into consideration in its deleteriousness assessment.
CADD Score The CADD score combines information from 63 different annotations including PhastCons, GERP, PhyloP, SIFT and PolyPhen, using a support vector machine classifier (Kircher et al, 2013). It measures deleteriousness by using observed variant frequency as the basis for its calculation. The C score ranges from 1 to 99, with a higher score indicating greater deleteriousness. Values >= 10 are predicted to be the 10% most deleterious substitutions, >= 20 indicate the 1% most deleterious.
Evidence Literary evidence gathered from ClinVar, OMIM, Locus Specific Databases, GWAS and COSMIC.

Filtering Flex Reports

Flex's mode of inheritance analysis is supported by the same rich filtering capabilities available in Variant Miner. See Filtering in Variant Miner for more information. 

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