Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline ATM sequence variants.

Autor:	Richardson ME; Ambry Genetics, Aliso Viejo, CA, USA. Electronic address: mrichardson@ambrygen.com., Holdren M; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Brannan T; Ambry Genetics, Aliso Viejo, CA, USA., de la Hoya M; Molecular Oncology Laboratory, Hospital Clínico San Carlos, IdISSC, 28040 Madrid, Spain., Spurdle AB; Population Health, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia., Tavtigian SV; Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Young CC; Ambry Genetics, Aliso Viejo, CA, USA., Zec L; Natera, Inc, San Carlos, CA, USA., Hiraki S; GeneDx, Gaithersburg, MD, USA., Anderson MJ; Invitae Corporation, San Francisco, CA, USA., Walker LC; Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand., McNulty S; Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Turnbull C; Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK., Tischkowitz M; Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK., Schon K; Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK., Slavin T; City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Foulkes WD; Departments of Human Genetics, McGill University, Montreal, QC, Canada., Cline M; UC Santa Cruz Genomics Institute, Mail Stop: Genomics, University of California, Santa Cruz, Santa Cruz, CA, USA., Monteiro AN; Department of Cancer Epidemiology, H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Pesaran T; Ambry Genetics, Aliso Viejo, CA, USA., Couch FJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. Electronic address: couch.fergus@mayo.edu.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2024 Sep 17. Date of Electronic Publication: 2024 Sep 17.
DOI:	10.1016/j.ajhg.2024.08.022
Abstrakt:	The ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer (HBOP) Variant Curation Expert Panel (VCEP) is composed of internationally recognized experts in clinical genetics, molecular biology, and variant interpretation. This VCEP made specifications for the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines for the ataxia telangiectasia mutated (ATM) gene according to the ClinGen protocol. These gene-specific rules for ATM were modified from the ACMG/AMP guidelines and were tested against 33 ATM variants of various types and classifications in a pilot curation phase. The pilot revealed a majority agreement between the HBOP VCEP classifications and the ClinVar-deposited classifications. Six pilot variants had conflicting interpretations in ClinVar, and re-evaluation with the VCEP's ATM-specific rules resulted in four that were classified as benign, one as likely pathogenic, and one as a variant of uncertain significance (VUS) by the VCEP, improving the certainty of interpretations in the public domain. Overall, 28 of the 33 pilot variants were not VUS, leading to an 85% classification rate. The ClinGen-approved, modified rules demonstrated value for improved interpretation of variants in ATM. Competing Interests: Declaration of interests M.J.A. was a paid employee of Invitae. M.E.R., T.B., T.P., and C.C.Y. were paid employees of Ambry Genetics. L.Z. was a paid employee of Natera. S.H. was a paid employee of GeneDx. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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