Development of Standards for DNA Sequence Variation Databases

A national project for the development of standards for DNA sequence variation databases was initiated by the RCPA in September 2013 in collaboration with the Human Genetics Society of Australasia (HGSA), and The Human Variome Project (HVP). The project is being funded through the Department of Health’s Quality Use of Pathology Program.

The Standards for clinical databases for genetic variants were approved by the RCPA Board on December 17, 2014.

A national project for the development of standards for DNA sequence variation databases was initiated by the RCPA in September 2013 in collaboration with the Human Genetics Society of Australasia (HGSA), and The Human Variome Project (HVP). The project is being funded through the Department of Health’s Quality Use of Pathology Program.

With the growing integration of emerging genetic technologies into diagnostic molecular genetic laboratories, there is a rapidly increasing volume of genetic tests, with increasing complexity becoming available as feasible investigative options for clinicians. These tests are producing an increasing quantity of genetic data requiring analysis and interpretation, which forms a substantial proportion of the workload associated with the test.

Historically, there has been the development of online mutation databases that are disease specific or locus specific (Locus Specific Databases – LSDB), often by research groups focused on the specific area. The existing databases are often inconsistent with variable quality due to variant call errors, and or inaccurate data submission. The quality of the interpretative aspects is often found wanting, with the pathogenicity of variants often incorrectly assigned. While the databases in existence have proved to be valuable research tools, there is a significant lack of appropriate databases that meet the robustness, reproducibility and stringent accuracy demanded of the clinical diagnostic environment. In addition to this, accessibility and sharing of the submitted data remains variable across databases. More widespread sharing of variants and associated phenotypes in a secure environment to protect the privacy of individual’s data, will allow the value of cumulative variant/phenotype information to be realised; accelerating the delivery of accurate, actionable, and timely clinical reports.

While there are several initiatives across the globe dedicated to the development and management of DNA data repositories, all are in early stages of evolution. There are currently no standards or an equivalent mechanism to accredit DNA sequence variation databases to ensure the accuracy and quality of data in any central repository meets the needs of the clinical diagnostics environment. Thus, the RCPA aims to develop standards in alignment with global initiatives that are workable standards in the rapidly changing genomics testing environment.

The objective of this project is to develop national standards to accredit DNA sequence variation data bases to ensure that the data bases are accurate and of sufficient quality to improve clinical decision making, counselling, and treatment planning by guiding:

  • Development of fit for purpose databases by diagnostic laboratories for efficient, informative analysis and interpretation of genetic variants
  • Access to and sharing of data whilst maintaining an individual’s privacy in a secure environment
  • The nature of data to be submitted; standardisation of terminology and ontology; and the functionality within the database

These standards will be written in the style of existing NPAAC standards and guidelines, a format which Australian diagnostic laboratories are familiar with through current laboratory accreditation processes.

The governance structure is intended to facilitate open communication and sharing of knowledge between all key stakeholder parties.

This will be achieved by engaging a steering committee with representation from RCPA, HVP, and HGSA, who will consider key issues to guide the development of a framework and draft standards. Terms of reference have been provided to the steering committee to provide them with guidance of expectations.

Following this, an expert consultation working group encompassing key stakeholders and knowledge rich individuals in specifically relevant fields will be invited to provide feedback and input to the standards and address any key issues that arise to aid in the development of the standards.

The standards will be released to the RCPA and HGSA membership for broader consultation following the completion of revision of the draft standards. The standards are scheduled to be completed in 2014. This will be monitored by the project officer through the work activity plan, scheduled key activity indicators, and scheduled submission of performance reports to the Department of Health.

Figure 1: Governance structure for project

Key deliverables of this project include:

  • Delivery of Standards for the Accreditation of DNA Sequence Variation Databases to RCPA and HGSA Councils for approval, to be utilised as standards for the membership
  • Submit the approved Standards to the Australian Department of Health at completion of the project

Following completion of the project:

  • The standards are to be presented to the National Pathology Accreditation Advisory Council (NPAAC) to seek endorsement to enable accreditation via the National Association of Testing Authorities / RCPA process
  • The standards will be promoted internationally through the HVP global network and other avenues.

The Steering committee has held two meetings by teleconference

October 2013 – A draft project implementation plan was presented, the outcome of which was a refining of the intended scope of the project to maintain focus.

February 2014 – A draft framework with options for key criteria was presented for discussion, the outcome of which was agreement on a 9 criteria framework to arrange the development of the draft standards. It is acknowledged that this framework may evolve as the standards develop.

June 2014 – A face to face steering committee meeting was held to critique and further develop the standards document prior to further consultation.

August 4 2014 – The project and draft standards document were presented and discussed at the Human Genetic Society of Australasia’s (HGSA) Annual Scientific Meeting.

August 18 2014 – A Consultation workshop (by invitation only) was held to seek broad and constructive input to the draft standards prior to further development and completion.

September 2 2014 – The Standards project was presented and discussed at the 10thAustralasian Mutation Detection Meeting

September 22-24 2014 – The Standards project was presented at the British Society of Genetic Medicine’s (BSGM) Annual Scientific Meeting.

October–November 2014 – A revised document was circulated to the steering committee and consultation workshop attendees for further feedback prior to the development of a final draft standards document.

December 17 2014 – The document "Standards for clinical databases of genetic variants" was approved by the RCPA board on December 17, 2014

The Steering Committee recently published “Quality standards for DNA sequence variation databases" to improve clinical management under development in Australia”. This document is open access and may be found at the following url:

The Standards for clinical databases of genetic variants document has now been approved for release.

February 27 – March 1 2015 – Standards will be presented and discussed at RCPA Pathology Update, Melbourne

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