PPM - Interpretation and Reporting of Copy Number Variants Detected by CMA in Constitutional Testing-Description and References

Description and References

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This document provides an overview of recommendations for the interpretation and reporting of copy number variants (CNVs) detected by chromosome microarray analysis (CMA) in constitutional testing. CMA has become the first-tier cytogenomic test for patients with intellectual disability, developmental delay, and congenital anomalies due to its increased diagnostic yield compared to traditional cytogenetic techniques. CMA not only detects copy number changes in the genome but also regions with absence of heterozygosity (AOH), which could indicate uniparental disomy or identity by descent. The American College of Medical Genetics and Genomics (ACMG) and ClinGen have published guidelines for reporting CNVs and AOH. The aim of this module is to encourage the use of these reporting guidelines for the interpretation and reporting of CNVs. Reporting AOH based on ACMG technical standards is addressed separately.<br /><br />The document also provides learning objectives, which include implementing analysis, interpretation, and reporting following ACMG guidelines of cytogenomic studies for patients with developmental delay and intellectual disability using microarray.<br /><br />The literature section of the document includes references to two relevant studies. The first study by Shao et al. discusses the technical standards of ACMG for chromosomal microarray analysis, including both constitutional and neoplastic disease applications. The second study by Riggs et al. provides joint consensus recommendations of ACMG and ClinGen for the interpretation and reporting of constitutional copy-number variants.<br /><br />Overall, this document serves as a guide for laboratory directors to choose cases of constitutional microarray with reportable CNVs and provides a framework for the work-up of these cases based on the ACMG and ClinGen guidelines. It emphasizes the importance of following these guidelines for accurate interpretation and reporting of CNVs detected by CMA in constitutional testing.

Keywords

interpretation

reporting

copy number variants

chromosome microarray analysis

constitutional testing

diagnostic yield

intellectual disability

developmental delay

congenital anomalies

absence of heterozygosity