TY - JOUR

T1 - AutoCNV

T2 - a semiautomatic CNV interpretation system based on the 2019 ACMG/ClinGen Technical Standards for CNVs

AU - Fan, Chunna

AU - Wang, Zhonghua

AU - Sun, Yan

AU - Sun, Jun

AU - Liu, Xi

AU - Kang, Licheng

AU - Xu, Yingshuo

AU - Yang, Manqiu

AU - Dai, Wentao

AU - Song, Lijie

AU - Wei, Xiaoming

AU - Xiang, Jiale

AU - Huang, Hui

AU - Zhou, Meizhen

AU - Zeng, Fanwei

AU - Huang, Lin

AU - Xu, Zhengfeng

AU - Peng, Zhiyu

N1 - Publisher Copyright: © 2021, The Author(s).

PY - 2021

Y1 - 2021

N2 - Background: The American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) presented technical standards for interpretation and reporting of constitutional copy-number variants in 2019 (the standards). Although ClinGen developed a web-based CNV classification calculator based on scoring metrics, it can only track and tally points that have been assigned based on observed evidence. Here, we developed AutoCNV (a semiautomatic automated CNV interpretation system) based on the standards, which can automatically generate predictions on 18 and 16 criteria for copy number loss and gain, respectively. Results: We assessed the performance of AutoCNV using 72 CNVs evaluated by external independent reviewers and 20 illustrative case examples. Using AutoCNV, it showed that 100 % (72/72) and 95 % (19/20) of CNVs were consistent with the reviewers’ and ClinGen-verified classifications, respectively. AutoCNV only required an average of less than 5 milliseconds to obtain the result for one CNV with automated scoring. We also applied AutoCNV for the interpretation of CNVs from the ClinVar database and the dbVar database. We also developed a web-based version of AutoCNV (wAutoCNV). Conclusions: AutoCNV may serve to assist users in conducting in-depth CNV interpretation, to accelerate and facilitate the interpretation process of CNVs and to improve the consistency and reliability of CNV interpretation.

AB - Background: The American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) presented technical standards for interpretation and reporting of constitutional copy-number variants in 2019 (the standards). Although ClinGen developed a web-based CNV classification calculator based on scoring metrics, it can only track and tally points that have been assigned based on observed evidence. Here, we developed AutoCNV (a semiautomatic automated CNV interpretation system) based on the standards, which can automatically generate predictions on 18 and 16 criteria for copy number loss and gain, respectively. Results: We assessed the performance of AutoCNV using 72 CNVs evaluated by external independent reviewers and 20 illustrative case examples. Using AutoCNV, it showed that 100 % (72/72) and 95 % (19/20) of CNVs were consistent with the reviewers’ and ClinGen-verified classifications, respectively. AutoCNV only required an average of less than 5 milliseconds to obtain the result for one CNV with automated scoring. We also applied AutoCNV for the interpretation of CNVs from the ClinVar database and the dbVar database. We also developed a web-based version of AutoCNV (wAutoCNV). Conclusions: AutoCNV may serve to assist users in conducting in-depth CNV interpretation, to accelerate and facilitate the interpretation process of CNVs and to improve the consistency and reliability of CNV interpretation.

KW - AutoCNV

KW - CNV classification

KW - CNV interpretation

KW - Scoring

U2 - 10.1186/s12864-021-08011-4

DO - 10.1186/s12864-021-08011-4

M3 - Journal article

C2 - 34615484

AN - SCOPUS:85116441374

VL - 22

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

M1 - 721

ER -