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International audience; The consistent and unambiguous description of sequence variants is essential to report and exchange information on the analysis of a genome. In particular, DNA diagnostics critically depends on accurate and standardized description and sharing of the variants detected. The sequence variant nomenclature system proposed in 2000 by the Human Genome Variation Society has been widely adopted and has developed into an internationally accepted standard. The recommendations are currently commissioned through a Sequence Variant Description Working Group (SVD-WG) operating under the auspices of three international organizations: the Human Genome Variation Society (HGVS), the Human Variome Project (HVP), and the Human Genome Organization (HUGO). Requests for modifications and extensions go through the SVD-WG following a standard procedure including a community consultation step. Version numbers are assigned to the nomenclature system to allow users to specify the version used in their variant descriptions. Here, we present the current recommendations, HGVS version 15.11, and briefly summarize the changes that were made since the 2000 publication. Most focus has been on removing inconsistencies and tightening definitions allowing automatic data processing. An extensive version of the recommendations is available online, at http://www.HGVS.org/varnomen

Here we argue that coor-dination of international efforts for develop -ing comprehensive mutation databases and patient phenotype registries is essential for optimal genetic health care.Well-funded international efforts for set -ting up mutation databases or registries are crucial for several reasons. Many variants that are found during clinical testing world-wide are not submitted to databases, where they could form an important resource for patient care. Many laboratories and clini-cians do not have the capacity or incentive to submit data to databases. This is espe-cially the case in developing countries owing mainly to technical insufficiency, lack of public awareness, lack of international com -munications, the absence of the concept of DNA biobanking, national authority restric -tions and lack of translation from original languages to English. The Human Variome Project (HVP) was initiated to facilitate the collection of all variants in all genes from all countries and to include annotation of these variants for pathogenicity and relevance to clinical medicine

Contains fulltext : 70182.pdf (Publisher’s version ) (Closed access) Genetic testing often results in the finding of a variant whose clinical significance is unknown. A number of different approaches have been employed in the attempt to classify such variants. For some variants, case-control, segregation, family history, or other statistical studies can provide strong evidence of direct association with cancer risk. For most variants, other evidence is available that relates to properties of the protein or gene sequence. In this work we propose a Bayesian method for assessing the likelihood that a variant is pathogenic. We discuss the assessment of prior probability, and how to combine the various sources of data into a statistically valid integrated assessment with a posterior probability of pathogenicity. In particular, we propose the use of a two-component mixture model to integrate these various sources of data and to estimate the parameters related to sensitivity and specificity of specific kinds of evidence. Further, we discuss some of the issues involved in this process and the assumptions that underpin many of the methods used in the evaluation process.