Dataset Information

Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study.

ABSTRACT:

Background

Array-CGH is the first-tier genetic test both in pre- and postnatal developmental disorders worldwide. Variants of uncertain significance (VUS) represent around 10~15% of reported copy number variants (CNVs). Even though VUS reanalysis has become usual in practice, no long-term study regarding CNV reinterpretation has been reported.

Methods

This retrospective study examined 1641 CGH arrays performed over 8 years (2010-2017) to demonstrate the contribution of periodically re-analyzing CNVs of uncertain significance. CNVs were classified using AnnotSV on the one hand and manually curated on the other hand. The classification was based on the 2020 American College of Medical Genetics (ACMG) criteria.

Results

Of the 1641 array-CGH analyzed, 259 (15.7%) showed at least one CNV initially reported as of uncertain significance. After reinterpretation, 106 of the 259 patients (40.9%) changed categories, and 12 of 259 (4.6%) had a VUS reclassified to likely pathogenic or pathogenic. Six were predisposing factors for neurodevelopmental disorder/autism spectrum disorder (ASD). CNV type (gain or loss) does not seem to impact the reclassification rate, unlike the length of the CNV: 75% of CNVs downgraded to benign or likely benign are less than 500 kb in size.

Conclusions

This study's high rate of reinterpretation suggests that CNV interpretation has rapidly evolved since 2010, thanks to the continuous enrichment of available databases. The reinterpreted CNV explained the phenotype for ten patients, leading to optimal genetic counseling. These findings suggest that CNVs should be reinterpreted at least every 2 years.

SUBMITTER: Ravel JM

PROVIDER: S-EPMC10204260 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study.

Ravel Jean-Marie JM Renaud Mathilde M Muller Jean J Becker Aurélie A Renard Émeline É Remen Thomas T Lefort Geneviève G Dexheimer Mylène M Jonveaux Philippe P Leheup Bruno B Bonnet Céline C Lambert Laëtitia L

Genome medicine 20230523 1

<h4>Background</h4>Array-CGH is the first-tier genetic test both in pre- and postnatal developmental disorders worldwide. Variants of uncertain significance (VUS) represent around 10~15% of reported copy number variants (CNVs). Even though VUS reanalysis has become usual in practice, no long-term study regarding CNV reinterpretation has been reported.<h4>Methods</h4>This retrospective study examined 1641 CGH arrays performed over 8 years (2010-2017) to demonstrate the contribution of periodicall ...[more]

PMID: 37221613

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Dataset Information

Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study.

Background

Methods

Results

Conclusions

Publications

Clinical utility of periodic reinterpretation of CNVs of uncertain significance: an 8-year retrospective study.

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