FAQs

Congenica displays a list of all patients, regardless of whether they are the proband, or if sequence data are available. As many patients have multiple family members the number of individuals listed in your GLH folders will be larger than the number of cases available for you to review.

This is currently not possible in Congenica. However, the patient table can be sorted by the “Proband” column, or filtered by SAP-ID to help you find the patients you wish to review.

Currently, only users with Clinical Data Curator permissions can do this. GLH users do not have this level of access. Please contact ge-servicedesk@genomicsengland.co.uk for further information.

Modifying these terms, or changing affected status of individuals will not result in an automatic re-analysis of the data by Genomics England.

The GLHs are responsible for selecting the most appropriate gene panel(s) based on the HPO terms and additional phenotypic information provided prior to being available in the Interpretation Portal. This initial selection of panels is used to generate the Tiering annotations.

Adding a new panel or filtering by a new pane will not alter any of the Tiering annotations provided by Genomics England. This would mean that high impact variants in genes on any new panels applied to the patient will not be flagged as tier 1 or tier 2.

In addition to Tier 1 and Tier 2 variants, all variants with decisions made against them are also presented on the Audit tab. If the primary reviewer has extended their analysis outside of Tier 1 and Tier 2, and recorded decisions against other variants, these will appear on the Audit tab.

Please contact the Genomics England Support Desk at ge-servicedesk@genomicsengland.co.uk. Please put “Clinical Result Query” in the email header and include the request ID (e.g. SAP-123-1) in the subject of the email, where possible.

By assigning any decision to a variant using one or more of the decision fields (“ACMG Classification”, “Pathogenicity”, “Contribution to Phenotype”, “Report Category” or “Confirmation Status”). This variant will then be included in the table in the “Audit” tab.

All variants classified as ‘Primary Finding’ will be included on the report. To remove a variant from your report, change the “Report category” field to ‘Do not Report’. To include a variant on your report, set the “Report category” field to ‘Primary Finding’.

The Sequence Alignments track is drawn using information from the BAM file and shows reads of all quality, including poor quality reads that would not be used for variant-calling. The Read Split metric is read from the VCF file, and only shows reads of good enough quality to be used for variant calling.

To identify variants in a specific gene or region of interest that is not covered by any of the panels available, search by gene or genomic coordinates. To access this feature, open the configuration menu (Figure 40), select the “Genes Location” filter, then select:

• “Specific Genes” to look for variants in one or more defined genes; use the search bar to look for the genes of interest
• “Genomic Region” and enter your genomic region of interest into the search bar

Genomics England and Congenica are both running the same version of Exomiser, however each uses different pathogenicty predictors

Click “Update” to update your filter parameters and return to the variants table.

Please note, it is not possible to filter simultaneously by Gene Panel, Specific Genes and Genomic Region; these options must be used independently.

We use hiPHIVE. Exomiser is not used by Congenica to filter variants in/out; this information is only used to sort the variants passing the other filters applied to the analysis. The different Exomiser scores can be described as follows:

• Exomiser Gene Combined Score: This is the overall Exomiser rank score combining the Exomiser Gene Pheno and Exomiser Gene Variant Scores ranges from 0 (benign) to 1 (pathogenic). this score can be used to prioritise the variants, where the higher the score the more pathogenic and phenotypically relevant the variant is predicted to be.
• Exomiser Gene Pheno Score: Generates a score between 0 (benign) to 1 (pathogenic) based on pairwise comparisons between HPO disease terms for the patient and the annotations present in the organism databases for the gene being assessed. It also compares patient HPO phenotype to that of nearby genes by protein-protein interaction network. This score can be used to prioritise the variants, where the higher the score the more pathogenic and phenotypically relevant the gene is predicted to be.
• Exomiser Gene Variant Score: This is a measure of how rare and pathogenic that variant is in the given gene. Variants are assigned a score between 0 (benign) to 1 (pathogenic).
• Exomiser Variant Score: The Exomiser Variant Score is a measure of how likely that variant is to be linked to the phenotypes specified. Variants are assigned a score between 0 (benign) to 1 (pathogenic).

Family clinical data are shown in the “Family” tab. This data is displayed as a pedigree and annotated with assigned HPO terms.

The analysis is restricted to the individual flagged as the Proband in the Genomics England Interpretation Request.

If a case has been blocked by Genomics England (e.g. as part of the QC process), or the original interpretation request contained errors, a new interpretation request is sent for the same family and the version of the SAP ID will be increased by one i.e. SAP-XXX-1 for the first interpretation request will become SAP-XXX-2 for the second interpretation request. The first version will not be viewable by the GLH.