PurposeThere is increasing demand from the public for direct-to-consumer (DTC) genetic tests, and the US Food and Drug Administration limits the type of health-related claims DTC tests can market. Some DTC companies provide raw genotyping data to customers if requested, and these raw data may include variants occurring in genes recommended by the American College of Medical Genetics and Genomics to be reported as incidental/secondary findings. The purpose of this study was to review the outcome of requests for clinical confirmation of DTC results that were received by our laboratory and to analyze variant classification concordance.MethodsWe identified 49 patient samples received for further testing that had previously identified genetic variants reported in DTC raw data. For each case identified, information pertaining to the outcome of clinical confirmation testing as well as classification of the DTC variant was collected and analyzed.ResultsOur analyses indicated that 40% of variants in a variety of genes reported in DTC raw data were false positives. In addition, some variants designated with the "increased risk" classification in DTC raw data or by a third-party interpretation service were classified as benign at Ambry Genetics as well as several other clinical laboratories, and are noted to be common variants in publicly available population frequency databases.ConclusionOur results demonstrate the importance of confirming DTC raw data variants in a clinical laboratory that is well versed in both complex variant detection and classification.GENETICS in MEDICINE advance online publication, 22 March 2018; doi:10.1038/gim.2018.38.

中文翻译：

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直接面向消费者的基因测试发布的假阳性结果突出了临床确认测试对适当患者护理的重要性。

目的公众对直接面向消费者 (DTC) 基因检测的需求不断增加，美国食品和药物管理局限制了 DTC 检测可以销售的与健康相关的声明类型。一些 DTC 公司应要求向客户提供原始基因分型数据，这些原始数据可能包括美国医学遗传学和基因组学学院推荐的基因中出现的变异，这些变异被报告为偶然/次要发现。本研究的目的是审查我们实验室收到的对 DTC 结果的临床确认请求的结果，并分析变异分类一致性。方法我们确定了 49 份收到的用于进一步测试的患者样本，这些样本先前已确定 DTC 原始报告中报告的遗传变异数据。对于确定的每个案例，收集和分析了与临床确认测试结果以及 DTC 变体分类有关的信息。结果我们的分析表明，在 DTC 原始数据中报告的各种基因中 40% 的变体是假阳性。此外，在 DTC 原始数据中或由第三方解释服务指定为“风险增加”分类的某些变体在 Ambry 遗传学以及其他几个临床实验室被归类为良性，并被指出是公开可用的常见变体人口频率数据库。结论我们的结果证明了在精通复杂变异检测和分类的临床实验室中确认 DTC 原始数据变异的重要性。《医学遗传学》高级在线出版物，2018 年 3 月 22 日；doi:10.1038/gim。