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dc.contributor.authorFeliubadaló, Lidia
dc.contributor.authorMolina Pineda Infantas, Ignacio Jesús
dc.identifier.citationLidia Feliubadaló, Alejandro Moles-Fernández, Marta Santamariña-Pena, Alysson T Sánchez, Anael López-Novo, Luz-Marina Porras, Ana Blanco, Gabriel Capellá, Miguel de la Hoya, Ignacio J Molina, Ana Osorio, Marta Pineda, Daniel Rueda, Xavier de la Cruz, Orland Diez, Clara Ruiz-Ponte, Sara Gutiérrez-Enríquez, Ana Vega, Conxi Lázaro, A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients, Clinical Chemistry, Volume 67, Issue 3, March 2021, Pages 518–533, []es_ES
dc.description.abstractBackground 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.es_ES
dc.description.sponsorshipFEDER funds-a way to build Europe PI19/00553 PI16/00563 PI16/01898 SAF2015-68016-Res_ES
dc.description.sponsorshipGeneralitat de Catalunya 2017SGR1282 2017SGR496es_ES
dc.description.sponsorshipCERCA Program: Government of Cataloniaes_ES
dc.description.sponsorshipXunta de Galiciaes_ES
dc.description.sponsorshipInstituto de Salud Carlos III. AES PI19/00340es_ES
dc.description.sponsorshipSpanish Government SAF2016-80255-Res_ES
dc.description.sponsorshipEuropean Commission EFA086/15es_ES
dc.description.sponsorshipInstituto de Salud Carlos III European Commissiones_ES
dc.publisherAmerican Association for Clinical Chemistry; Oxford University Presses_ES
dc.rightsAtribución 3.0 España*
dc.subjectHereditary canceres_ES
dc.subjectVariant classificationes_ES
dc.subjectACMG/AMP guidelineses_ES
dc.subjectSpanish databasees_ES
dc.titleA Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patientses_ES

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Atribución 3.0 España
Except where otherwise noted, this item's license is described as Atribución 3.0 España