Update "VCEP Impact Report Nov 30 2023"

[dazzariti]

As discussed on 9/5 Broad ClinGen Weekly meeting

Update the "VCEP Curated Variants Calculations April 2022"

Ask: The goal is to compare the overall classification in ClinVar PRIOR to a ClinGen VCEP submission, compared to the overall status with today’s current VCEP classification

https://docs.google.com/spreadsheets/d/1narS_N7kmkTl8OM1B7JRZqpZtTzf4QPjCthKIMz6hsw/edit?usp=sharing

[dazzariti]

Clarified the plan with Heidi:

Update the data in this sheet https://docs.google.com/spreadsheets/d/1narS_N7kmkTl8OM1B7JRZqpZtTzf4QPjCthKIMz6hsw/edit?usp=sharing on the "VCEP variants" tab (this would be a task for Larry and Ryan, I'm joining their meeting tomorrow and can discuss)

Once updated data is available, someone on the Broad/ClinGen team update the data Kelsea put together https://docs.google.com/spreadsheets/d/1u1Bitj4ClcbOGbSa5pM_VeN8ikZiQfbOwpVfqUXonUw/edit?usp=sharing - specifically the "Classification Changes After EP Assertion" pie chart - the goal is to compare the overall classification in ClinVar PRIOR to ClinGen VCEP submission, compared the overall status with today’s current VCEP classification

Based on the results of that exercise, we'll determine if it's still necessary to identify all the pilot variants and remove them from the analysis

[dazzariti]

@larrybabb @RyanFWebb Danielle and Larry discussed this today, here is some clarification.

We would like to compare the overall classification in ClinVar PRIOR to a ClinGen VCEP submission, compared to the overall status with today’s current VCEP classification. It is updating the work done in this sheet but it does not need to be completed in the same format if there is a more straightforward way to do it (i.e. the "VCEP Variants" tab does not need to be reproduced if it is easier to start fresh).

Detailed ask -

For any variant record in ClinVar that has a ClinGen VCEP SCV, what was the overall classification prior to the first ClinGen VCEP submission on that record, compared to the overall classification today.

Example:

https://www.ncbi.nlm.nih.gov/clinvar/variation/616/

Prior to the ClinGen PAH VCEP submission, this record had an overall clinical significance of "Conflicting interpretations of pathogenicity" https://www.ncbi.nlm.nih.gov/clinvar/variation/VCV000000616.1/ - today the overall clinical significance in ClinVar is "Likely Pathogenic" https://www.ncbi.nlm.nih.gov/clinvar/variation/616/

[larrybabb]

@dazzariti I created a new script that I hope we can just use going forward. Here's the first draft https://docs.google.com/spreadsheets/d/1gsl19l95JdCSD2HWSmoovkKhGRRo3nDWOUlaH5i3hEI/edit#gid=1654405943 It's just a result set of the 5K+ SCVs that VCEPs have in clinvar as of 11/26/2023. I created a read.me page to explain the data in the report. I think that this should give us a lot to use for generating graphs and reports. But like everything we should probably show it to Heidi and the group and get feedback. If there's no major change to this then I can make this updateable by the users, right now it's static. Let me know what you think.

[dazzariti]

@larrybabb Before doing too much with this report to make it undateable, could you generate again with the latest ClinVar data release? https://docs.google.com/spreadsheets/d/1gsl19l95JdCSD2HWSmoovkKhGRRo3nDWOUlaH5i3hEI/edit#gid=1654405943