Transcript CCMG_2015_ppt_final - Canadian Open Genetics Repository

Updates and Upcoming Collaborations
CCMG Meeting September 2015
Agenda
1. COGR overview
2. Updates
3. Current variant numbers
4. BRCA Manuscript
4. Discussion
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
Workflow Overview
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
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
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
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)
22 GeneInsight Instances Created
Organization
Alberta Children's Hospital, Calgary AB
Atlantic Cancer Research Institute
British Columbia Cancer Agency, Vancouver BC
Children’s & Women’s Health Centre of BC, Vancouver BC
Children's Hospital of Eastern Ontario, Ottawa ON
Credit Valley Hospital, Trillium Health Centre, Mississauga ON
Dept of Medical Genetics, University of Alberta, Edmonton AB
Hamilton Health Sciences, McMaster University, Hamilton ON
Impact Genetics Inc., Bowmanville ON
Izaak Walton Killam Health Centre, Dalhousie University, Halifax NS
Kingston General Hospital, Queen’s University, Kingston ON
McGill University Health Complex, Montréal QC
Memorial Health University Medical Center, St. John’s NL
Mount Sinai Hospital, University of Toronto, Toronto ON
North York General Hospital, Toronto ON
Ontario Institute of Cancer Research (OICR), Toronto ON
Regional Health Authority, University of Manitoba, Winnipeg MB
Sainte-Justine Hospital, University of Montreal, Montréal QC
SickKids Hospital and McLaughlin Centre, Toronto ON
University Hospital, Western University, London ON
Women's College Hospital, University of Toronto, Toronto ON
*Also sharing with VariantWire
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Sharing Status
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COGR Variant Numbers
COGR 2014 and 2015 Comparison
8000
7000
6000
5000
4000
3000
2000
1000
0
Total Number of Variants
2014
2015
3802
7766
Total Number of Copy Number
Variants
3340
3340
COGR Gene and Disease Numbers
COGR 2014 and 2015 Comparison
100
90
80
70
60
50
40
30
20
10
0
2014
2015
Total Number of Genes
56
90
Total Number of Diseases
13
60
Number of COGR Variants (≥5) by Clinically Linked Disease
2000
1800
1600
1400
1200
1000
800
600
400
200
0
COGR Shared Classification Data To Date
Variant Classification
Number of Variants
Pathogenic
2116
Likely Pathogenic
205
Variant of Unknown Significance
1097
Likely Benign
328
Benign
673
Unclassified
2476
Consistent Interpretations
Agree
219
Pathogenic or Likely Pathogenic
12
Benign or Likely Benign
46
Total Consistent Interpretations
277
Different Interpretations
(Likely) Pathogenic vs. VUS
19
(Likely) Benign vs. VUS
39
(Likely) Pathogenic vs. (Likely) Benign
75
Total Different Interpretations
133
June 2015 Consensus Call
• Overall discrepant variant classifications did not change after
consensus call
• Proposal for moving forward:
1.
2.
Present collected evidence in ACMG guideline format
Ask discrepant lab(s) to review and re-assess variant classification
• Goal:
• Gather agreement that evidence based from ACMG guidelines is correct
• Suggestions?
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 14th!
• Discrepancy report will be sent out at the end of September 2015
COGR BRCA Variant Numbers To Date
1600
1400
1200
1000
800
600
400
200
0
BRCA1
BRCA 2
Ben
178
209
Likely Ben
87
105
VUS
251
307
Likely Path
15
21
Path
762
741
Unclassified
23
22
Grand Total
1316
1405