The standardization of variant curation criteria is essential for accurate interpretation of genetic results and clinical care of patients. The variant curation guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 are widely used but are not gene specific. To address this issue, the Clinical Genome Resource (ClinGen) Variant Curation Expert Panels (VCEP) have been tasked with developing gene-specific variant curation guidelines. The Glaucoma VCEP was created to develop rule specifications for genes associated with primary glaucoma, including myocilin (MYOC), the most common cause of Mendelian glaucoma. Of the 28 ACMG/AMP criteria, the Glaucoma VCEP adapted 15 rules to MYOC and determined 13 rules not applicable. Key specifications included determining minor allele frequency thresholds, developing an approach to counting probands and segregations, and reviewing functional assays. The rules were piloted on 81 variants and led to a change in classification in 40% of those that were classified in ClinVar, with functional evidence influencing the classification of 18 variants. The standardized variant curation guidelines for MYOC provide a framework for the consistent application of the rules between laboratories, to improve MYOC genetic testing in the management of glaucoma.

中文翻译：

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肌纤蛋白的 ACMG/AMP 变体管理指南规范：克林根青光眼专家小组的建议

变异处理标准的标准化对于准确解释遗传结果和患者的临床护理至关重要。由美国医学遗传学和基因组学学院 (ACMG) 和分子病理学协会 (AMP) 于 2015 年制定的变异管理指南被广泛使用，但不是基因特异性的。为了解决这个问题，临床基因组资源 (ClinGen) 变异管理专家小组 (VCEP) 的任务是制定基因特异性变异管理指南。青光眼 VCEP 的创建是为了制定与原发性青光眼相关的基因的规则规范，包括肌纤蛋白( MYOC )，这是孟德尔青光眼的最常见原因。在 28 个 ACMG/AMP 标准中，青光眼 VCEP 将 15 个规则改编为MYOC并确定了13条规则不适用。关键规范包括确定次要等位基因频率阈值、开发一种计算先证者和分离的方法，以及审查功能测定。这些规则在 81 个变体上进行了试点，并导致 40% 的 ClinVar 分类变体的分类发生变化，功能证据影响了 18 个变体的分类。MYOC的标准化变异管理指南为实验室之间规则的一致应用提供了一个框架，以改进青光眼管理中的MYOC基因检测。