![Page 1: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/1.jpg)
Meeting summary and thoughts
Garry Cutting, MDMcKusick Nathans Institute of Genetic Medicine
Johns Hopkins
sharing data · reducing diseasean NGO Official Partner of UNESCO
![Page 2: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/2.jpg)
KudosScientific Programme CommitteeRichard G. H. Cotton (Melbourne, Australia)Raymond Dalgleish (Leicester, United Kingdom)Johan T. den Dunnen (Leiden, Netherlands)Marc Greenblatt (Burlington, VT, United States)Aida Falcon de Vargas (Caracas, Venezuela)Finlay Macrae (Melbourne, Australia)Martina Witsch-Baumgartner (Innsbruck, Austria)
Organising SecretariatRania Horaitis, ICOHeather Howard, ICOHelen Robinson , ICOTimothy Smith, ICOCasimiro Vizzini, UNESCO
![Page 3: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/3.jpg)
And finish on time
Don’t be boring
![Page 4: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/4.jpg)
Annotating variation in the human genome
• The challenge
• Potential solutions
The Cambridge Wine Blogger http://cambridgewineblogger.blogspot.com/2011/06/on-breadth-vs-depth-in-tasting.html
![Page 5: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/5.jpg)
Stylianos Antonarakis, Session VIII
![Page 6: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/6.jpg)
![Page 7: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/7.jpg)
![Page 8: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/8.jpg)
![Page 9: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/9.jpg)
Rapid increase in the number of genes associated with mendelian phenotypes
Source: OMIMYears
Num
ber o
f gen
es
![Page 10: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/10.jpg)
Number of variants reported per gene in the Leiden Open Variation Database (LOVD)
Variants from LOVD databases version 2.0-24 or higher and with properly configured reference sequences were used to extract the number of unique alleles reported per gene. If a gene was present in multiple databases (duplicate instances), the raw data was parsed such that the highest number of variants per a given gene was reported. Data courtesy of Ivo F.A.C. Fokkema and Johan T. den Dunnen.
Figures courtesy of Melissa Lee Cutting GR AJHG 2014
![Page 11: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/11.jpg)
• Increasing number of genes associated with mendelian disease
• Increasing number of variants per gene
Perfect Storm of Variants
![Page 12: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/12.jpg)
Interpretive gap: Difference between rate of variant discovery and rate of
variant annotation
Variants identified Interpretive gap
Annotated
Cost of sequencing
Time
$$
Cutting GR AJHG 2014
![Page 13: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/13.jpg)
Quantifying the interpretive gap
CFTR
137 for OMIM, 1301 for HGMD, 345 for LOVD
HBA1HBB
Gene matched counts of variants per gene, sorted by length
![Page 14: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/14.jpg)
Christopher Cassa, Session X
![Page 15: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/15.jpg)
![Page 16: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/16.jpg)
Stylianos Antonarakis, Session VIII
![Page 17: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/17.jpg)
Thomy de Ravel, Session II
![Page 18: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/18.jpg)
Nik Nor Liza Nik Hassan, Session II
![Page 19: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/19.jpg)
Raj Ramesar, Session III
![Page 20: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/20.jpg)
Dwomoa Adu, Session III
![Page 21: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/21.jpg)
Enock Matovu, Session III
![Page 22: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/22.jpg)
Stylianos Antonarakis, Session VIII
![Page 23: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/23.jpg)
Ted Kalbfleisch, Session IV
![Page 24: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/24.jpg)
Moris Swertz, Session IV
![Page 25: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/25.jpg)
Stylianos Antonarakis, Session VIII
![Page 26: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/26.jpg)
![Page 27: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/27.jpg)
Peter Taschner, Session V
![Page 28: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/28.jpg)
Raymond Dalgleish, Session V
![Page 29: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/29.jpg)
Ada Hamosh, Session V
![Page 30: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/30.jpg)
Stylianos Antonarakis, Session VIII
![Page 31: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/31.jpg)
Hoan Nyugen, Session VIII
![Page 32: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/32.jpg)
Tuuli Lappalainen, Session VIII
![Page 33: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/33.jpg)
Variant Annotation Projects
• INSiGHT: International Society for Gastrointestinal Hereditary Tumors – Mismatch repair genes (Thompson et al Nat Genet 2014)
• CFTR2: Clinical and Functional Translation of CFTR – CFTR (Sosnay et al Nat Genet 2013)
• ENIGMA :Evidence-based Network for the Interpretation of Germline Mutant Alleles– BRCA 1/2
sharing data · reducing diseasean NGO Official Partner of UNESCO
![Page 34: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/34.jpg)
Maurizio Genuardi, Session IX
![Page 35: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/35.jpg)
Finlay Macrae, Session IX
![Page 36: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/36.jpg)
Christopher Cassa, Session X
![Page 37: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/37.jpg)
![Page 38: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/38.jpg)
Standards Development & Recommended Systems
• HGVS variation nomenclature• Mutalyzer • LOVD• VarioML • Variation Ontology (VariO)
• W01:Disclaimer Statements on G/DSDBs• WG02: Assigning Pathogenicity to a Genetic Variant• WG03 Minimal content for gene variant databases (LSDBS)• WG04 Minimum Content Requirements for HVP Country Nodes• WG05: Variant Database Quality Assessment• WG06: Disease &Phenotype Descriptions in Gene/Disease Specific
Databases
sharing data · reducing diseasean NGO Official Partner of UNESCO
![Page 39: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/39.jpg)
Summary
![Page 40: HVP5: Meeting summary and thoughts - Garry Cutting](https://reader033.vdocuments.net/reader033/viewer/2022042814/554ea2e6b4c9055f7b8b485b/html5/thumbnails/40.jpg)
Thank you for attending HVP5
sharing data · reducing diseasean NGO Official Partner of UNESCO