ClinGen 遗传性乳腺癌、卵巢癌和胰腺癌 (HBOP) 变异管理专家小组 (VCEP) 由临床遗传学、分子生物学和变异解释领域的国际公认专家组成。该 VCEP 根据 ClinGen 协议，为美国医学遗传学会和分子病理学协会 (ACMG/AMP) 共济失调毛细血管扩张突变 (ATM) 基因指南制定了规范。这些 ATM 基因特定规则是根据 ACMG/AMP 指南进行修改的，并在试点管理阶段针对不同类型和分类的 33 个 ATM 变体进行了测试。试点显示 HBOP VCEP 分类和 ClinVar 存款分类之间达成了多数协议。六个试点变体在 ClinVar 中的解释相互矛盾，并且根据 VCEP 的 ATM 特定规则重新评估，结果是 VCEP 将四个变体分类为良性，一个分类为可能致病，一个分类为意义不确定 (VUS) 的变体，从而改善了公共领域解释的确定性。总体而言，33 个试点变体中有 28 个不是 VUS，分类率为 85%。 ClinGen 批准的修改后的规则证明了对改进 ATM 中变体解释的价值。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

The ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer (HBOP) Variant Curation Expert Panel (VCEP) is composed of internationally recognized experts in clinical genetics, molecular biology, and variant interpretation. This VCEP made specifications for the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines for the ataxia telangiectasia mutated (ATM) gene according to the ClinGen protocol. These gene-specific rules for ATM were modified from the ACMG/AMP guidelines and were tested against 33 ATM variants of various types and classifications in a pilot curation phase. The pilot revealed a majority agreement between the HBOP VCEP classifications and the ClinVar-deposited classifications. Six pilot variants had conflicting interpretations in ClinVar, and re-evaluation with the VCEP's ATM-specific rules resulted in four that were classified as benign, one as likely pathogenic, and one as a variant of uncertain significance (VUS) by the VCEP, improving the certainty of interpretations in the public domain. Overall, 28 of the 33 pilot variants were not VUS, leading to an 85% classification rate. The ClinGen-approved, modified rules demonstrated value for improved interpretation of variants in ATM.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.