Small Variant Grid¶
This page provides the ability to:
- Review the germline small variants identified by DRAGEN
- Review additional annotations and linkouts to external resources for each variant (see Variant Grid Guide below for further details)
- Exclude, or assign an ACGS classification to a variant (for further details see the recording interpretation page)
- Select a transcript and contribution to phenotype for a variant, and add a comment
Variant Grid Guide¶
Key
| # | Section | Description |
|---|---|---|
| 1 | Actions | Actions including "View Details" - viewing the variant details page, flagging, adding to export PDF and adding comments. |
| 2 | Tier | Tier. This can be 'Tier 1', 'Tier 2', 'Tier 3', or blank for variants that do not fall within a gene. When clicking on the tooltip next to the tier, a card opens with details of the panel applied, the gene, the variant segregation, variant mode of inheritance, and penetrance |
| 3 | Variant info | The VCF format of the variants, and a button which displays a linkout to IGV (for read depth investigation) and links to external databases and resources (DECIPHER, gnomAD, UCSC, VarSome and SpliceAI) for the variant, and a button to copy the variant coordinates in Alamut format |
| 4 | Genes | HGNC gene symbol(s) which the variant affects. We show the affected genes in the highest tier (additional genes at lower tiers are indicated with a +n icon, with n being the number of genes). If there are multiple genes at the highest tier, these are displayed on separate lines within the row, in no particular order. If the gene is green in PanelApp, it is highlighted green. Clicking on the genes opens a card containing further information about the gene, including Ensembl IDS for the canonical transcript, gene and protein, the c. HGVS nomenclature for the CDS change, the p. HGVS nomenclature for the protein change, and links to external resources for the gene (OMIMM, PubMed, PanelApp and ClinGen) |
| 5 | Most severe change | Contains the c. and p. HGVS nomenclature for the transcript with the most severe change for that variant. The flag to the right indicates whether the change is the most severe change (S), or whether it is the change for the MANE Select (M) or MANE Plus Clinical (M+) transcripts. If multiple transcripts have the most severe consequence, then the change displayed in the grid is selected based on the following priority order:
|
| 6 | Consequences | Predicted consequence types (SO terms) for transcripts that have a consequence matching the most severe consequence for the gene, and any consequences for MANE Select and MANE Plus Clinical transcripts. The flag to the right of the consequence indicates whether the consequence is associated with any MANE Select (M) or MANE Plus Clinical (M+) transcripts, or whether it is the most severe consequence for the gene (S). N.B. multiple consequences can be associated with the same transcript. |
| 7 | Max Allele Frequency | Maximum allele frequency for the variant across GnomAD and GEL internal studies |
| 8 | Alt & Homozygotes total count | Displays the number of homozygous genotypes for the subpopulation with the max allele frequency (number of individuals within the population dataset that are homozygous for the variant) and number of alt alleles for the subpopulation with the max allele frequency (number of times the variant is observed within the population dataset) for the variant. N.B. number of alt alleles is not available for the GEL dataset |
| 9 | Proband / Mother / Father etc. | A column for the proband and one per family member, containing the zygosity symbols, and ref/alt read split information. More details can be found in the segregation card on the Variant Details page for the variant. On hover over the zygosity symbols, the affected status of the individual is displayed ('X Affected', 'X Unaffected' or 'X Uncertain') |
| 10 | ClinVar | Clinvar ID entry of the variant. Clicking the ClinVar icon will show the variant in ClinVar |
| 11 | QC Flag | Flags that indicate a variant call may be of a lower quality and at greater risk of being a false positive. Hover over the QC flag for a description. Refer to the variant details documentation for a complete list of QC flags |
| 12 | Classification | The assigned ACGS tiering of a variant. Click the pill to add or edit the classification of a variant (for further details see the recording interpretation page) |
Sorting¶
By default, all variants are sorted by tier and coordinates. 20 variants are shown by default, and more are loaded dynamically when scrolling to the bottom of the page.
Currently the New IB does not support custom sorting of variants.