checking the experts: compliance with author instructions regarding hgvs nomenclature and variant...
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Checking the expertsCompliance with author instructions regarding HGVS nomenclature and database submission
6th Human Variome Project meeting, June 2, 2016
Zgjim Osmani, student-assistant [email protected]
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IntroductionAim: Improving quality of genetic variant & phenotype descriptions
Author instructions:
HGVS nomenclature Yes/No?
Database submission Yes/No?
January 2016 issues of genetics journals
Sharing reliable information for diagnostic use
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Genetic testing in Amsterdam: 178 nationalitiesMigration challenges DNA diagnostics
Problem:Different populationshave different variants:effects unknown,characterized as VUS
Solution:World-wide data sharing
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Material & Methods
Human Variome Project’s Journal List
Check the variant flowchart
HGVS nomenclature: Mutalyzer Name Checker tool
Extra attention: Reference sequences & RNA analysis
Students of the University of Applied Sciences Leiden
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Material & Methods DNA – Day
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Variant terminology Reference sequences
Total of 126 articlesRelevant: 59 articles
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12% contains incorrect DNA variant descriptions
RNA descriptionsreported for 1% of variants only
31% of variantssubmitted to databases
Variant descriptions summaryNumber of articles: 59
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8Leiden Muscular Dystrophy pages (www.DMD.nl) Johan den Dunnen
c.636C>T r.(636c>u) p.(=) Prediction:Coding synonymous
Muscular Dystrophy PatientDatabase provides information about variant effects
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9Leiden Muscular Dystrophy pages (www.DMD.nl) Johan den Dunnen
Muscular Dystrophy PatientDatabase provides information about variant effects
c.636C>T r.535_652del p.Asp179Valfs*23
RNA analysis:Different effect than predicted!
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Review and database curation is important!Variant in article:
NM_002778.2(PSAP_v001): c.777_778ins24 (no RNA description) p.Met259_Gln260ins8
Cesani et al. (2016), Mutation update of ARSA and PSAP genes causing Metachromatic Leukodystrophy, Human Mutation, 16 – 27.
Variant in database:
Exon boundary: NG_009301.1(PSAP_v001): c.777_777+1ins… ?NG_009301.1(PSAP_v001): c.778-1_778ins… ?
Insertion of 33 nucleotidesUnchecked Mutalyzer Position Converter result?
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• Genomic reference sequences frequently omitted
• RNA descriptions not mentioned
• Reviewers & editors could help to improve quality:Reject manuscripts not following the authors instructions
Conclusions
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Jeroen F. J. LarosKoen van DiemenJulia. A Lopez Hernandez
DNA day Hackathon Team: Floyd Wittink Samuel van Apeldoorn Sabine BlekerWessel BomJasper BoomMark uit het BroekDavy Cats
Leonie Didden
Jolanda EssensHendrik FreieGuido GrootIlke van den HoekMarten HoogeveenMidia KhalifaLisa KnijnenburgMelanie KooijAnnemijn Manger
Thomas OlivierAaricia van Oostrom
Kevin van RooijenLieke Schoenmaker, Matthias Tammes BuirsOlga VethTim SmithRozemarijn van der Vooren
Acknowledgments
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Results
Human Mutation January ‘16Total Articles Total
VariantsNM_Refse
q Protein Predictions Using the word "Mutation"
14 192 8 of 9 162 8 of 9Genomic and
Genetic Articles Checked
Novel Variant
NG_Refseq
HGVS Protein Predictions
Using the word "Variant"
9 61 0 of 9 156 (96%) 8 of 9
New individuals
HGVS Variants NP_Refseq RNA Change
ManuscriptUsing the word "Polymorphism
"70 186 (97%) 1 of 9 1 4 of 9
Phenotype Submission
Variant Submission NC_Refseq RNA Change
Database43 (61%) 63 (33%) 1 of 9 30
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American Journal of Human Genetics January ‘16
Total Articles Total Variants
NM_Refseq Protein Predictions Using the word
"Mutation"16 52 5 of 5 29 5 of 5
Genomic and Genetic Articles Checked
Novel Variant
NG_Refseq
HGVS Protein Predictions
Using the word "Variant"
5 36 0 of 5 28 (97%) 5 of 5
New individuals
HGVS Variants NP_Refseq RNA Change
ManuscriptUsing the word "Polymorphism
"72 51 (98%) 1 of 5 0 2 of 5
Phenotype Submission
Variant Submission NC_Refseq RNA Change
Database45 (63%) 34 (65%) 0 of 5 0
Results
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ResultsEuropean Journal of Human Genetics
January ‘16Total Articles Total
VariantsNM_Refse
q Protein Predictions Using the word "Mutation"
26 103 8 of 8 96 4 of 8Genomic and
Genetic Articles Checked
Novel Variant
NG_Refseq
HGVS Protein Predictions
Using the word "Variant"
8 42 2 of 8 96 (100%) 8 of 8
New individuals
HGVS Variants NP_Refseq RNA Change
ManuscriptUsing the word "Polymorphism
"215 103
(100%) 4 of 8 6 3 of 8
Phenotype Submission
Variant Submission NC_Refseq RNA Change
Database132 (61%) 93 (90%) 1 of 8 76