In genomics, the clinical application of Next Generation Sequencing technologies (such as Whole Genome or Exome Sequencing) has attracted considerable attention from UK policymakers, interested in the benefits such technologies could bring the National Health Service. However, this boosterism plays little attention to the challenges raised by a kind of result known as a Variant of Uncertain Significance, or VUS, which require clinical geneticists and related colleagues to classify ambiguous genomic variants as 'benign' or 'pathogenic'. With a rigorous analysis based on data gathered at 290 clinical meetings over a two-year period, this paper presents the first ethnographic account of decision-making around NGS technology in a NHS clinical genomics service, broadening our understanding of the role formal criteria play in the classification of VUS. Drawing on Stefan Timmermans' concept of 'reflexive standardisation' to explore the way in which clinical genetics staff classify such variants this paper explores the application of a set of criteria drafted by the American College of Medical Genetics and Genomics, highlighting the flexible way in which various resources - variant databases, computer programmes, the research literature - are drawn on to reach a decision. A crucial insight is how professionals' perception of, and trust in, the clinical practice at other genomics centres in the NHS, shapes their own application of criteria and the classification of a VUS as either benign or pathogenic.

中文翻译：

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基因组临床中的反射性标准化和不确定性的解决。


在基因组学领域，下一代测序技术（例如全基因组或外显子组测序）的临床应用引起了英国政策制定者的极大关注，他们对此类技术可以给国家卫生服务带来的好处感兴趣。然而，这种支持很少关注一种被称为“意义不确定的变异”（VUS）的结果所带来的挑战，该结果要求临床遗传学家和相关同事将模糊的基因组变异分类为“良性”或“致病性”。本文基于两年内 290 次临床会议收集的数据进行了严格分析，首次提出了 NHS 临床基因组学服务中 NGS 技术决策的人种学解释，拓宽了我们对正式标准在临床基因组学服务中的作用的理解。 VUS 的分类。本文借鉴 Stefan Timmermans 的“反射标准化”概念来探索临床遗传学人员对此类变异进行分类的方式，本文探讨了美国医学遗传学和基因组学学院起草的一套标准的应用，强调了分类的灵活方式。各种资源——不同的数据库、计算机程序、研究文献——被用来做出决定。一个重要的见解是专业人士对 NHS 其他基因组学中心临床实践的看法和信任如何形成他们自己的标准应用以及 VUS 良性或致病性的分类。