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2023 ACMG Annual Clinical Genetics Meeting Digital ...
Updating patient results for genomic CNVs intersec ...
Updating patient results for genomic CNVs intersecting dosage sensitive genes on the ACMG secondary findings v3.1 list
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Pdf Summary
This document describes a process for reevaluating previously detected copy number variants (CNVs) involving genes on the ACMG secondary findings v3.1 list. The goal of the reevaluation is to update reports with accurate clinical risk information. The process involves querying a database for CNVs overlapping with ACMG genes, reviewing genes for dosage sensitivity, determining if the CNV disrupts the gene, and updating reports if necessary. The document includes examples of CNVs involving the PALB2 and TMEM127 genes. <br /><br />The results of the reevaluation show that out of 67 CNVs involving ACMG genes, 33 were copy number gains and 34 were copy number losses. No updated reports were issued for the copy number gains as the genes involved were not triplosensitive. However, 11 cases with copy number losses required updated reports. These included cases involving the TMEM127 gene, where the reports were updated to include risk for hereditary paraganglioma-pheochromocytoma syndrome, and cases involving PALB2, where reports were updated to include risk for hereditary breast and/or ovarian cancer. One case involving FLNC required an updated report to include risk for dilated cardiomyopathy. <br /><br />The process of reevaluating CNVs is important for providing updated clinical risk information. In this study, 10 patients received updated reports with information on potential risks for hereditary cancer or dilated cardiomyopathy. This information can be useful for screening, intervention, and communicating with at-risk family members. However, a limitation of this study is that the ACMG SF 3.1 gene list is primarily based on sequence variant data, not CNV data. The document suggests that future iterations of the ACMG SF gene lists should consider including dosage sensitivity data. Overall, the process described in this study improves the accuracy of reported CNVs and enhances patient care.
Asset Subtitle
Co-Author - Zoe K. Lewis, MS, CGC; Co-Author - Daniel P. Reich, PhD; Presenting Author - Denise I. I Quigley, PhD;
Meta Tag
array CGH
Microarray
Molecular Cytogenetics
Susceptibility Locus
Variant Detection
Co-Author
Zoe K. Lewis, MS, CGC
Co-Author
Daniel P. Reich, PhD
Presenting Author
Denise I. I Quigley, PhD
Keywords
copy number variants
ACMG secondary findings v3.1
reevaluation process
clinical risk information
database querying
dosage sensitivity
gene disruption
updated reports
PALB2 gene
TMEM127 gene
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