@misc{10481/68014,
year = {2021},
month = {3},
url = {http://hdl.handle.net/10481/68014},
abstract = {Background

Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene.
Methods

Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants.
Results

Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%.
Conclusions

Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.},
organization = {FEDER funds-a way to build Europe 
	
PI19/00553
PI16/00563
PI16/01898
SAF2015-68016-R},
organization = {Generalitat de Catalunya
	
2017SGR1282
2017SGR496},
organization = {CERCA Program: Government of Catalonia},
organization = {Xunta de Galicia},
organization = {Instituto de Salud Carlos III. AES 
	
PI19/00340},
organization = {Spanish Government
	
SAF2016-80255-R},
organization = {European Commission
	
EFA086/15},
organization = {Instituto de Salud Carlos III

European Commission},
publisher = {American Association for Clinical Chemistry; Oxford University Press},
keywords = {Hereditary cancer},
keywords = {Variant classification},
keywords = {ACMG/AMP guidelines},
keywords = {Spanish database},
title = {A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients},
doi = {10.1093/clinchem/hvaa250},
author = {Feliubadaló, Lidia and Molina Pineda Infantas, Ignacio Jesús},
}