1. CCMG Meeting September 2015 Updates and Upcoming Collaborations

2. Agenda 1.COGR overview 2.Updates 3.Current variant numbers 4.BRCA Manuscript 4. Discussion

3. COGR Objectives To create Canada’s unified, open-access, clinical-grade genetic database using a commonly shared platform Collaborative effort for the collection, sharing and analysis of variants reported by medical diagnostic laboratories across Canada To create variant classification consensus among clinical laboratories through data sharing and analysis To standardized variant assessment procedures and disseminate results to a large public data repository

4. Workflow Overview

5. Update: Routine Variant Uploads Goal: Quarterly with discrepancy reports Now have additional informatics support Semi-automate export pre-processing Alamut export = Instantaneous upload Other = Customize script

6. Update: Variant Assessment Tool 5.0 Release coming soon! What’s new Restructured with improved organization Now can directly import and export VAT from GeneInsight

7. Update: Public facing website Coming Winter of 2016! Open access resource for general audience Patients and family members at risk Portal to query diseases and associated genes linked to diseases Current variant classification Consensus

8. Update: Funding 3-year OGI grant is expiring Received additional funding to secure year 4 of COGR Applied for funding to link COGR with other collaborative efforts such as the Global Alliance for Genomics and Heath (GA4GH)

9. 22 GeneInsight Instances Created Organization Upload StatusSharing Status Alberta Children's Hospital, Calgary ABUploadedSharing Atlantic Cancer Research InstitutePending- British Columbia Cancer Agency, Vancouver BCUploading- Children’s & Women’s Health Centre of BC, Vancouver BCPending- Children's Hospital of Eastern Ontario, Ottawa ONUploadedSharing* Credit Valley Hospital, Trillium Health Centre, Mississauga ONUploadedSharing Dept of Medical Genetics, University of Alberta, Edmonton ABUploading- Hamilton Health Sciences, McMaster University, Hamilton ONUploading- Impact Genetics Inc., Bowmanville ONPending- Izaak Walton Killam Health Centre, Dalhousie University, Halifax NSPending- Kingston General Hospital, Queen’s University, Kingston ONUploadedSharing McGill University Health Complex, Montréal QCUploaded- Memorial Health University Medical Center, St. John’s NLPending- Mount Sinai Hospital, University of Toronto, Toronto ONUploadedSharing* North York General Hospital, Toronto ONUploadedSharing Ontario Institute of Cancer Research (OICR), Toronto ONUploadedSharing Regional Health Authority, University of Manitoba, Winnipeg MBUploading- Sainte-Justine Hospital, University of Montreal, Montréal QCUploading- SickKids Hospital and McLaughlin Centre, Toronto ONUploadedSharing University Hospital, Western University, London ONPending- Women's College Hospital, University of Toronto, Toronto ONUploadedSharing* * Also sharing with VariantWire

10. COGR Variant Numbers

11. COGR Gene and Disease Numbers

12. Number of COGR Variants (≥5) by Clinically Linked Disease

13. COGR Shared Classification Data To Date Variant ClassificationNumber of Variants Pathogenic2116 Likely Pathogenic205 Variant of Unknown Significance1097 Likely Benign328 Benign673 Unclassified2476 Consistent Interpretations Agree219 Pathogenic or Likely Pathogenic12 Benign or Likely Benign46 Total Consistent Interpretations277 Different Interpretations (Likely) Pathogenic vs. VUS19 (Likely) Benign vs. VUS39 (Likely) Pathogenic vs. (Likely) Benign75 Total Different Interpretations133

14. June 2015 Consensus Call Overall discrepant variant classifications did not change after consensus call Proposal for moving forward: 1.Present collected evidence in ACMG guideline format 2.Ask discrepant lab(s) to review and re-assess variant classification Goal: Gather agreement that evidence based from ACMG guidelines is correct Suggestions?

15. BRCA Manuscript BRCA variant collaboration as an example of the power of data sharing in Canada Currently have interest from Alberta, British Columbia, Manitoba Ontario and Quebec BRCA1/2 variant data submission deadline is September 14 th ! Discrepancy report will be sent out at the end of September 2015

16. COGR BRCA Variant Numbers To Date