Internet Archive Scholar

Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants

Kristy Lee, Kate Krempely, Maegan E. Roberts, Michael J. Anderson, Fatima Carneiro, Elizabeth Chao, Katherine Dixon, Joana Figueiredo, Rajarshi Ghosh, David Huntsman, Pardeep Kaurah, Chimene Kesserwan (+16 others)
2018 Human Mutation  

Preserved Fulltext

fulltext thumbnail
Web Archive Capture PDF (726.6 kB)
https://web.archive.org/web/20200208111233/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6188664&blobtype=pdf

A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL. The file type is application/pdf.

The variant curation guidelines published in 2015 by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) provided the genetics community with a framework to assess variant pathogenicity; however, these rules are not genespecific. Germline pathogenic variants in the CDH1 gene cause hereditary diffuse gastric cancer and lobular breast cancer, a clinically challenging cancer predisposition syndrome that often requires a multidisciplinary
more » ... of experts to be properly managed. Given this challenge, the Clinical Genome Resource (ClinGen) Hereditary Cancer Domain prioritized the development of the CDH1 Variant Curation Expert Panel (VCEP) to develop and implement rules for CDH1 variant classifications. Here we describe the CDH1 specifications of the ACMG/AMP guidelines, which were developed and validated after a systematic evaluation of variants obtained from a cohort of clinical laboratory data encompassing ~827,000 CDH1 sequenced alleles. Comparing previously reported germline variants that were classified using the 2015 ACMG/AMP guidelines to the CDH1 VCEP recommendations resulted in reduced variants of uncertain significance and facilitated resolution of variants with conflicted assertions in ClinVar. Overall, the ClinGen CDH1 VCEP recommends the use of these CDH1-specific guidelines for the assessment and classification of variants identified in this clinically actionable gene.
doi:10.1002/humu.23650 pmid:30311375 pmcid:PMC6188664 fatcat:atmxyuxg5nhi3bnzq2fwobfmla
Citation

Kristy Lee, Kate Krempely, Maegan E. Roberts, Michael J. Anderson, Fatima Carneiro, Elizabeth Chao, Katherine Dixon, Joana Figueiredo, Rajarshi Ghosh, David Huntsman, Pardeep Kaurah, Chimene Kesserwan, Tyler Landrith, Shuwei Li, Arjen R. Mensenkamp, Carla Oliveira, Carolina Pardo, Tina Pesaran, Matthew Richardson, Thomas P. Slavin, Amanda B. Spurdle, Mackenzie Trapp, Leora Witkowski, Charles S. Yi, Liying Zhang, Sharon E. Plon, Kasmintan A. Schrader, Rachid Karam. "Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline CDH1 sequence variants." Human Mutation 39.11 (2018) 1553-1568