Additional Findings Results¶
As part of the consent process to join the 100,000 Genomes Project participants were asked if they wanted their genome sequence to be analysed for additional health information, referred to as “additional findings”, which are not related to the primary reason that the participant joined the Project.
Detailed information can be found here.
Viewing 100K Additional Findings Case List¶
Once logged in to the 100K Portal, click on “Additional Findings” on the green banner.
Users can use the search bar at the top of the page to search for a specific participant ID, family ID, or primary findings case ID.
Info
Unlike rare disease primary findings, which are reported per family, additional findings are reported per individual participant. i.e. if consented, each partipant in a 100K Rare Disease Family (e.g. mum, dad, proband) has a seperate additional findings result reported
Or users can use the filters to narrow down the list.
Filtering the Cases
| # | Section | Description |
|---|---|---|
| 1 | Patient Summary | The Referral ID for the patient. |
| 2 | Referral Priority | Priority for the case, e.g. “Routine” or “Urgent”. |
| 3 | Case Status | Interpretation Status of the case, e.g. whether or not it is has a SoF ready. |
| 4 | Workflow status | The workflow status for the referral. |
| 5 | Patient | Link out to TOMS. If available, PID will be queried from TOMS and displayed here. |
| 6 | Interpretation Flags | This flag describes the TINC status of the sample. |
| 7 | Interpretation Services | List of the interpretation services that have been applied to the case. |
| 8 | Sex | The sex of the patient. |
| 9 | Patient Choice | Yes- patient has agreed to the test, No- patient has declined the test, NA- patient choice not relevant. |
| 10 | Interpreting Organisation | Defined during test ordering. |
| 11 | Requesting Organisation | Defined during test ordering. |
| 12 | Notes | Notes added to the case during Test Order. |
| 13 | DSS | For example, Illumina BaseSpace Variant Interpreter (BSVI) for cancer referrals. |
| 14 | Tumour Local ID | Information about the Tumour types; primary or metastatic; presentation and other details about the tumour. |
| 15 | Tumour Content | Tumour content is displayed as High, Medium or Low with an accompanying tumour content percentage. The thresholds for High, Medium and Low are as follows: Low is <40% tumour content. Medium is 40-60%. High is >60%. Please note that the tumour content displayed here in the Portal is the content entered by the GLH at the point of test order. |
A list of cards showing additional findings participants will be shown and are summarised in table below.
Participants Overview
| Key | Description |
|---|---|
| 1 | The Additional Findings ID in format AF- |
| 2 | The participant ID, Family ID, Year of Birth, Sex and Requesting organisation is shown here. |
| 3 | This section shows the date the additional findings case was created, last modified and the genome assembly for the case. |
| 4 | This tag tells the user about the status of the primary findings (PF) for this participant. |
| 5 | This tag tells the user about the status of the additional findings (AF) for this participant. |
| 6 | This tag tells the user about the consent status this participant has for health-related findings, and whether variants have been identified.* Hover over the tag for more information. |
| 7 | The tag tells the user about the consent status this participant has for reproductive |
The flag indicates consent status ( green = opted in, red = opted out, grey* = not applicable)
The box to the left of the flag indicates if variants have been identified. ( tick = possible findings identified, cross = no possible findings identified, dash = variants not yet analysed)
Reviewing Additional Findings data for a participant¶
To access an individual participant page, users should click on the additional findings ID.
This will lead to a participant page detailing the participant’s details and the variant(s) found.
Warning
The participant page will only be accessible if the participant has consented to additional findings AND there are variants identified.
On the participant page, users will see the “Participant Summary” displayed below.
Participant Summary
| Key | Description |
|---|---|
| 1 | The Additional Findings ID for the participant. |
| 2 | The individual patient ID. |
| 3 | The status of this additional findings case. |
| 4 | The status of the linked primary findings case for this participant (whether the participant is a proband (rare disease and cancer) or relation to the proband (rare disease only)). |
| 5 | The interpretation services which have been applied to this participant’s genome. For additional findings cases, this will be the ‘genomics_england_additional_findings’ interpretation service. |
| 6 | The site under which the participant was recruited to the 100,000 Genomes Project. |
| 7 | The participant’s consent status for health-related and reproductive findings. In the example shown, the participant has given consent for health related but not reproductive findings analysis. |
| 8 | The genome assembly for the participant’s genome. |
| 9 | The year of birth for the participant. |
| 10 | The sex of the participant. |
| 11 | For rare disease cases, there is a link out to CVA for the case this participant is a member of for primary findings (the clinical indication under which the person(s) was recruited). |
| 12 | A link to the primary findings case associated to this participant. |
Under the participant data summary, there is a table indicating the clinical indication being considered for analysis. For all additional findings analyses, the clinical indication will be “additional findings” and the affiliated panels will be the latest versions of the additional findings panels that have been applied, as displayed in the diagram below. The panels used in the analysis indicate whether the analysis was performed for adult or childhood conditions and whether analysis of copy number variants was performed.
The additional findings participant summary page also includes an ‘Interpretation Summary’, similar to the interpretation summary seen in primary findings analysis. This lists the number of SNVs/Indels and CNVs detected by the additional findings reporting logic in the participant’s genome and the number of unique variants. The results are split into ‘health related’ and ‘reproductive’.
A summary of findings is available to download for each participant which will list the variant(s) detected in the participant’s genome. If no variants were found, no summary of findings is available to download. The summary of findings is automatically populated with all additional findings detected for a participant.
If variants are found, there will be an exit questionnaire to populate via the “Review” button beside the “Download” button for the summary of findings. See section below for more details.
Summmary of Findings Buttons
| Key | Description |
|---|---|
| 1 | Downloading the Summary of Findings for additional findings. |
| 2 | Link to the exit questionnaire for additional findings. |
Summary of Findings¶
In the additional findings summary of findings, users will find participant information, a statement of the gene panel(s) applied in the analysis for the participant, information of the variant(s) found, the report context and the report annex which lists the referenced databases and software versions used in the analysis.
Summary of Findings HTML
| Key | Description |
|---|---|
| 1 | The participant ID. |
| 2 | The date and time the additional findings summary of findings was generated. |
| 3 | The 3-digit code correlating to the NHS Genomic Medicine Centre affiliated with the participant. |
| 4 | The participant’s additional findings ID. |
| 5 | A link out to the clinical summary for the participant in Labkey. |
| 6 | The participant information table includes the family ID (where applicable), individual ID, sample number, year of birth and gender for the participant |
| 7 | This table illustrates the gene panels which have been applied in the analysis. The panels listed here indicate whether the analysis was performed for adult or childhood conditions. |
If a relevant variant is found within a gene listed on the additional findings panel applied, the variant will be returned in the summary of findings with more information.
SoF Variants
| Key | Description |
|---|---|
| 1 | The gene name. |
| 2 | The genomic position of the variant (chromosome:position). |
| 3 | The variant found. |
| 4 | The HGVS annotation for the variant if available. Annotation is provided for all transcripts (GENCODE Basic transcripts Ensembl version 90) |
| 5 | The ACMG classification for this variant, if available. |
| 6 | The predicted consequence of this variant according to CellBase. |
| 7 | Any PubMed IDs in support of the variant being flagged. |
Once the summary of findings has been reviewed by a user, the exit questionnaire must then be completed to close the additional findings case. Users can navigate to the outcomes questionnaire by clicking on the “Review” button next to the relevant version of the summary of findings.
Reviewing variants in IGV¶
To review variants in IGV, users may follow the link to the primary findings section of the Interpretation from the participant page from where IGV.js can be accessed directly.
Alternatively, the URL for accessing IGV for a selected sample can be constructed using the following format by replacing the sample ID (LP number) shown in bold with the sample ID of the relevant participant.
Users can then navigate to the region of interest within the IGV browser.
-
For rare disease participants with genomes aligned to GRCh38: study=
1000000032https://igv.genomicsengland.nhs.uk/?study=1000000032&samples=**LPXXXXXX**®ion=chr1:1-1001 -
For rare disease participants with genomes aligned to GRCh37: study=
1000000024https://igv.genomicsengland.nhs.uk/?study=1000000024&samples=**LPXXXXXX**®ion=chr1:1-1001 -
For cancer participants: study=
1000000034https://igv.genomicsengland.nhs.uk/?study=1000000034&samples=**LPXXXXXX**®ion=chr1:1-1001
If the link is not working
Alternatively, if the IGV link obtained from the Interpretation Portal is not working, you can replace the cohort ID with the samples ids, as following:
https://igv.genomicsengland.nhs.uk/?study=1000000032&cohorts=114000928_1®ion=chr1:1482179-1482379 >> would become >> https://igv.genomicsengland.nhs.uk/?study=1000000032&samples=LP3000220-DNA_A10,LP3000325-DNA_E10,LP3000227-DNA_F10®ion=chr1:1482179-1482379
Outcomes Questionnaire¶
The exit questionnaire asks the user for more information about the variants returned in the summary of findings.
Variant questions¶
Users should submit their exit questionnaires to close the additional findings case.
Did you carry out technical confirmation of this variant via an alternative test?
A question asking the user if they carried out technical confirmation of the variant via an alternative test. There is a drop-down for this question, with the options: “Yes”, “No”, “NA”.
Did the test confirm that the variant is present?
A question asking the user if the test they performed confirmed if the variant was present. There is a drop-down for this question, with the options: “Yes”, “No”, “NA”.
Did you include the variant in your report to the clinician?
A question asking the user if the variant was included in the report to the clinician. There is a drop-down for this question, with the options: “Yes”, “No”, “NA”.
What ACMG pathogenicity score (1-5) did you assign to this variant?
A question asking the user which ACMG pathogenicity score was assigned to the variant. There is a drop-down for this question, with the options: “pathogenic_variant”, “likely_pathogenic_variant”, “variant_of_unknown_clinical_significance”, “likely_benign_variant”, “benign_variant” and “not_assessed”.
Please provide PMIDs for papers which you have used to inform your assessment for this variant, separated by a ; for multiple papers.
A section in which users can provide PMIDs for papers which they have used to inform their assessment of the variant.
Entity Group questions¶
Users also need to answer ‘Entity Group Questions’ which ask about the participant.
Does this patient have a positive family history relevant to this condition?
A question asking the user if the patient has a positive family history related to the condition the gene variant is associated with. There is a drop-down for this question, with the options: “Yes”, “No”, “Unknown”.
Was this variant previously known to be present in this patient?
A question asking the user if the variant was already previously known to be present in this patient. There is a drop-down for this question, with the options: “Yes”, “No”, “Unknown”.
Was this variant previously known to be present in this family?
A question asking the user if the variant was previously known to be present in the patient’s family. There is a drop-down for this question, with the options: “Yes”, “No”, “Unknown”.
Has the clinical team identified any changes to clinical care which could potentially arise as a result of this variant/variant pair?
A question asking the user if the clinical team has identified any changes to clinical care which could potentially arise as a result of this variant/variant pair. There is a radio checkbox system for users to select one or more answers from the following: ‘change_in_medication’, ‘surgical_option’, ‘additional_surveillance_for_proband_or_relatives’, ‘clinical_trial_eligibility’, ‘informs_reproductive_choice’, ‘other’, ‘unknown’, ‘none’"
After the summary of findings has been reviewed and all questions in the exit questionnaire have been populated, the user can “Submit” their questionnaire by clicking on the “Submit” button at the bottom of the exit questionnaire page. This will close the additional findings case. Cases with no additional findings are automatically closed and no summary of findings or exit questionnaire will be available to review. The questionnaire may be saved and submitted at a later date by clicking on “Save draft” if preferred.