Setting Normative Function: Identification of areas where Standards and Guidelines are required
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Transcript of Setting Normative Function: Identification of areas where Standards and Guidelines are required
SETTING NORMATIVE FUNCTION: IDENTIFICATION OF AREAS WHERE STANDARDS AND GUIDELINES ARE REQUIRED
Standards: systems, procedures, technologies that HVP determined shall be used
Guidelines: systems, procedures, technologies that HVP determined to be beneficial to adopt
Arleen AUERBACH
Raymond DALGLEISH
Mauno VIHINEN
Finlay MACRAY
Mireille CLAUSTRES
DATABASE QUALITY AND DATA QUALITY/RELIABILITY
How to ensure data accuracy?
How to avoid data redundancy?
How to ensure nomenclature checking?
How to ensure quality assurance (to organize EQC?)
What is the role of the HVP in database quality?
What is the role of biomedical journals in ensuring variant reporting standards?
SYSTEMATICS of DATABASESLogical database checks (e.g. dates) Ontologies, nomenclatures, vocabularies...
The role of the CURATOR: towards a new concept of a profession with a career structure (ex. a core health service?)
PATHOGENICITY ASSESSMENT (PA) and REPORTING
Familial segregation of variants and associated phenotype?
Annotation (functional significance: in vitro, in vivo and in silico analyses?)
How much phenotype must be attached to data? define a clinical form?
How to accommodate incomplete or variable penetrance in PA?
How to assess polyvariant mutants (modifiers of mutations)?
How to establish the frequency of variants in patients and controls?(ex. 2 patients in a family: how many times the allele is
reported?)
Integration of sometimes discrepant information?
Updating pathogenicity (may change with time)/state of knowledge of VUS
ETHICAL AND LEGAL ISSUESCountry-specific framework approval?Signed Consent Forms (autonomy protection) (PROSPECTIVE)?Capacity of an individual to consent for submission of the family pedigree data?Anonymisation (privacy protection) vs. medical and scientific interest?
ETHNIC QUALIFICATIONSShould they be population definitions or geographical locations? Founder effects?
INTELLECTUAL PROPERTY RIGHTSHow to protect curators and submitters against misuse?Need to define clarity of data use policy with respect to diagnostic vs. research?
LINKS WITH INDUSTRY AND PRIVATE LABSConditions of access and commercialisation
Database name
URL resource
Contact information (e-mail)
Date resource established
Conditions of use (free or type of license)
Curation policy and curator’s identity
Standards used (gene/symbol/chr. location/
link to RefSeq, ontologies, vocabularies)
Data formats
Data accessibility/output options
Data release policy and frequency
Data submission policy
Documentation available
Relevant publications
Tools available
Disclaimer
CORE DESCRIPTION (HVP recommendations already published)
Patient/family ID (anonymous/encrypted)
Sex
Ethnicity/geographic location
Gene/variant/protein
Clinical Phenotype
Case-control (number of affected/unaffected
carriers and controls
Frequency of the variant in the population(s)
Co-segregation with disease
Allelic status (homozygous, heterozygous, hemizygous)
Co-occurring variants
Detection technique and year of testing
Testing coverage (which genes/exons were tested)
Nomenclature
GOVERNANCE and MANAGEMENTOversight roles and responsibilitiesCharter to regulate relationship with third parties?Medical/legal responsibilities?Dispute resolution?Sustainability and funding
STANDARDS COMPLIANCE and DATA EXCHANGEInteraction between Country Nodes and gene/disease-specific databases (LSDBs)
Scope: purposes of the DB and data types captured QMS (quality management system?)Country-specific framework approval obtained Nature and source of financing or funding
CORE DESCRIPTION : additional HVP recommendations to be formulated ?