Aarabi Mahmoud, Darabi Helia, Bashar Aryan, Bellissimo Daniel, Rajkovic Aleksandar, Yatsenko Svetlana A
Departments of Pathology, and Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Medical Genetics and Genomics Laboratories, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA.
Genet Med Open. 2024 Mar 13;2:101839. doi: 10.1016/j.gimo.2024.101839. eCollection 2024.
To determine the pathogenicity and frequency of copy-number variants (CNV) in the 81 secondary finding (SFv3.2) genes recommended by the American College of Medical Genetics and Genomics (ACMG).
Review of published evidence on pathogenicity of partial or complete copy-number losses or gains in ACMG SFv3.2 was performed. Frequency of reportable CNVs in the ACMG SFv3.2 genes was investigated among 10,959 patients tested by chromosomal microarray analysis in a single academic testing laboratory at the University of Pittsburgh Medical Center during 2011 to 2023.
We identified 58 ACMG SFv3.2 genes for which sufficient evidence supports reporting of partial or complete copy-number losses as secondary findings. On the contrary, reporting of copy-number gains was not supported by evidence in any of the ACMG SFv3.2 genes. Overall, CNVs in SFv3.2 genes were detected in 32 of 10,959 (0.29% or 1 in 343) patients in our cohort.
This study provides a framework for consistent reporting of CNVs, detected by chromosomal microarray analysis, exome, or genome sequencing, in any of the ACMG SFv3.2 genes. To our knowledge, this is the largest cohort of patients studied for estimation of frequency of reportable CNVs in the ACMG SFv3.2 genes.
确定美国医学遗传学与基因组学学会（ACMG）推荐的81个二级发现（SFv3.2）基因中拷贝数变异（CNV）的致病性和频率。
对已发表的关于ACMG SFv3.2中部分或完全拷贝数缺失或增加的致病性证据进行综述。在2011年至2023年期间，于匹兹堡大学医学中心的一个学术检测实验室对10959名接受染色体微阵列分析检测的患者，调查ACMG SFv3.2基因中可报告CNV的频率。
我们鉴定出58个ACMG SFv3.2基因，有充分证据支持将部分或完全拷贝数缺失报告为二级发现。相反，在任何ACMG SFv3.2基因中，均无证据支持报告拷贝数增加。总体而言，在我们队列的10959名患者中，有32名（0.29%或1/343）检测到SFv3.2基因中的CNV。
本研究为通过染色体微阵列分析、外显子组或基因组测序检测到的ACMG SFv3.2基因中CNV的一致报告提供了一个框架。据我们所知，这是为估计ACMG SFv3.2基因中可报告CNV频率而研究的最大患者队列。
