2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-<em>ATM</em> and <em>PALB2</em> Variant Curation Guidelines Progress Update: ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer Variant Curation Expert Panel

ATM and PALB2 Variant Curation Guidelines Progress Update: ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer Variant Curation Expert Panel

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This document provides an update on the progress of the ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer Variant Curation Expert Panel (HBOP VCEP) in developing gene-specific modifications of the ACMG/AMP sequence variant classification guidelines for breast, ovarian, and pancreatic cancer predisposition genes. The panel consists of experts from various institutions and laboratories and aims to provide guidance for future variant classification and clarify discrepancies in variant classifications. The FDA-approved process for variant classification allows the HBOP VCEP to resolve discrepant classifications in ClinVar. <br /><br />The document highlights the challenges in variant classification for hereditary cancer genes due to the multifactorial etiology of cancer and incomplete penetrance, which often leads to a lack of consensus in classification. The classification of variants of uncertain significance (VUS) is crucial for maximizing diagnostic yield and appropriately managing cancer surveillance and treatment. The HBOP VCEP uses an FDA-approved process for rule drafting and variant classification to refine the general ACMG/AMP classification rules and address discrepancies between diagnostic laboratories.<br /><br />The steps involved in the formation and work of the HBOP VCEP are outlined, including the drafting of gene-specific specifications, pilot assessments of variants using the guidelines, and sustained curation of variants. The document also provides contact information for those interested in joining the panel.<br /><br />Overall, this document describes the ongoing efforts of the HBOP VCEP to develop gene-specific variant curation guidelines for ATM and PALB2 and highlights the importance of standardized variant classification in the field of hereditary cancer genetics.

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Presenting Author - Megan Holdren, MS, CGC; Co-Author - Marcy E. Richardson, BS, PhD; Co-Author - Deborah I. Ritter, PhD; Co-Author - Colin C. Young, PhD; Co-Author - Terra Brannan, PhD; Co-Author - Tina Pesaran, MS, CGC; Co-Author - Lauren Zec, MS, CGC; Co-Author - Susan Hiraki, MS, CGC; Co-Author - Michael Anderson, PhD; Co-Author - Melissa Southey, PhD; Co-Author - Clare A. Turnbull, MD, PhD; Co-Author - Marc Tischkowitz, MBBS, PhD; Co-Author - Huma Q. Rana, MD, MPH; Co-Author - Shannon M. McNulty Gray, PhD; Co-Author - Sean V. Tavtigian, PhD; Co-Author - Logan C. Walker, PhD; Co-Author - William D. Foulkes, MBBS, PhD; Co-Author - Alvaro NA. Monteiro, PhD; Co-Author - Sarah E. Brnich, MD, PhD; Co-Author - Melissa S. Cline, PhD; Co-Author - Amanda B. Spurdle, PhD; Co-Author - Miguel de la Hoya, PhD; Co-Author - Fergus J. Couch, PhD;

Meta Tag

Cancer Syndromes

Genetic Testing

Co-Author Marcy E. Richardson, BS, PhD

Co-Author Deborah I. Ritter, PhD

Co-Author Colin C. Young, PhD

Co-Author Terra Brannan, PhD

Co-Author Tina Pesaran, MS, CGC

Co-Author Lauren Zec, MS, CGC

Co-Author Susan Hiraki, MS, CGC

Co-Author Michael Anderson, PhD

Co-Author Melissa Southey, PhD

Co-Author Clare A. Turnbull, MD, PhD

Co-Author Marc Tischkowitz, MBBS, PhD

Co-Author Huma Q. Rana, MD, MPH

Co-Author Shannon M. McNulty Gray, PhD

Co-Author Sean V. Tavtigian, PhD

Co-Author Logan C. Walker, PhD

Co-Author William D. Foulkes, MBBS, PhD

Co-Author Alvaro NA. Monteiro, PhD

Co-Author Sarah E. Brnich, MD, PhD

Co-Author Melissa S. Cline, PhD

Co-Author Amanda B. Spurdle, PhD

Co-Author Miguel de la Hoya, PhD

Co-Author Fergus J. Couch, PhD

Presenting Author Megan Holdren, MS, CGC

Keywords

ClinGen

Hereditary Breast

Ovarian Cancer

Pancreatic Cancer

Variant Curation Expert Panel

ACMG/AMP

variant classification

variants of uncertain significance

diagnostic laboratories

standardized variant classification