2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Reinterpretation of Postnatal Clinical Copy Number Variants: A Practical Approach for Implementation as a Routine Laboratory Practice

Pdf Summary

This document describes a practical approach to the implementation of routine laboratory practices for the reinterpretation of postnatal clinical copy number variants (CNVs). The laboratory developed a chromosomal microarray database with more than 10 years of CNV data to facilitate searches. They reviewed CNVs from 2011-2021 that met specific criteria and were able to identify cases for reevaluation. The reevaluations typically required a case-level review. The laboratory developed standardized processes for initiating internal reevaluations and responding to external reevaluation requests, including issuing amended reports and recontacting healthcare providers.<br /><br />The document highlights the need for high-quality variant interpretation practices in clinical laboratories, particularly for CNVs. CNVs are difficult to standardize due to technical limitations and inconsistent classification practices. The authors present the results of a multi-year initiative to implement routine laboratory- and provider-initiated CNV reevaluation processes in an academic reference laboratory setting.<br /><br />The document concludes that laboratory processes for updating CNV interpretations over time require comprehensive yet efficient methods for identifying and reevaluating CNVs. The authors observed a high frequency of clinically significant CNV reclassifications from the laboratory-initiated reevaluation process. This supports the need for practical approaches to variant reevaluation in order to optimize patient care.<br /><br />The document also provides criteria for reclassifying CNVs, issuing amended reports, and recontacting the ordering provider. It discusses the results of laboratory-initiated and provider-initiated reevaluations, showing the percentage of cases that were reclassified as clinically significant or not clinically significant, as well as cases that were unchanged.<br /><br />In summary, the document highlights the importance of implementing routine laboratory practices for the reinterpretation of CNVs. It provides insights and best practices based on the experiences of a large academic reference laboratory. The findings demonstrate the need for practical approaches to variant reevaluation in order to improve patient care.

Asset Subtitle

Presenting Author - Zoe K. Lewis, MS, CGC; Co-Author - Daniel P. Reich, PhD; Co-Author - Timothy Tidwell, PhD; Co-Author - Benjamin I. Clyde, MS, MB(ASCP)cm; Co-Author - Scott Zobell, Technologist; Co-Author - Erica F. Andersen, PhD, FACMG; Co-Author - Denise I. I Quigley, PhD;

Meta Tag

Variant Detection

Policy Issues

Microarray

Genetic Testing

Databases

Clinical Cytogenetics

array CGH

Co-Author Denise I. I Quigley, PhD

Co-Author Erica F. Andersen, PhD, FACMG

Co-Author Scott Zobell, Technologist

Co-Author Benjamin I. Clyde, MS, MB(ASCP)cm

Co-Author Timothy Tidwell, PhD

Co-Author Daniel P. Reich, PhD

Presenting Author Zoe K. Lewis, MS, CGC

Keywords

routine laboratory practices

reinterpretation

postnatal clinical copy number variants

chromosomal microarray database

CNV data

reevaluation

standardized processes

variant interpretation practices

academic reference laboratory

variant reevaluation