Deborah Ritter
Abstract
Deborah Rittera, Eric Duncavageb, Julia Elvinc, Frampton Garrettc, Obi L. Griffithb, Malachi Griffithb, Katherine Janewayd, Laura MacConailld, Matthew McCoye, Funda Meric-Bernstamf, Jason Merkerg, Charles Mullighanh, Donald Parsonsi, Keyur Patelf, Gordana Racaj, Erin Ramosk, Jason Rosenbauml, Somak Roym, Angshumoy Royi, Dmitriy Sonkinn, Alex Wagnero, Jeremy Warnerp, Sharon Plonj, Marilyn Liq, Shashikant Kulkarnii
aBaylor College of Medicine, Houston, TX, USA; bWashington University, St. Louis, MO, USA; cFoundation Medicine, Cambridge, MA, USA; dDana Farber Cancer Institute, Boston, MA, USA; eGeorgetown University, Washington, DC, USA; fThe University of Texas MD Anderson Cancer Center, Houston, TX, USA; gUniversity of North Carolina at Chapel Hill, Chapel Hill, NC, USA; hSt. Jude Children’s Research Hospital, Memphis, TN, USA; iBaylor College of Medicine, Houston, TX, USA; jChildren’s Hospital Los Angeles, Los Angeles, CA, USA; kNational Human Genome Research Institute, Bethesda, MD, USA; lKaiser Permanente Northern California Regional Genetics Labo, Berkeley, CA, USA; mDivision of Pathology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; nNational Cancer Institute, Bethesda, MD, USA; oNationwide Children’s Hospital, Columbus, OH, USA; pVanderbilt University Medical Center, Nashville, TN, USA; qChildren’s Hospital of Philadelphia, Philadelphia, PA, USA
The Clinical Genome Resource (ClinGen) Somatic Working Group (WG) is actively developing a somatic cancer variant curation expert panel (SC-VCEP) process that parallels the process developed by ClinGen for monogenic disorders. A critical aspect of the latter is the Sequence Variant Interpretation (SVI) WG, which provides guidance on applying the ACMG/AMP classification framework and VCEP specification approval. The ClinGen Somatic Cancer Variant Interpretation Committee (CVI) is a parallel effort to provide input and oversight in developing specifications based on the AMP/ASCO/CAP somatic variant interpretation guidelines.
The CVI has 30 members, with representation from academic institutions and commercial laboratories and broad expertise from oncologists, pathologists, clinicians, clinical/laboratory geneticists, researchers and informaticians. The Somatic WG has three SC-VCEPs in the 4-step expert panel process (see abstract from Saliba et al). The CVI has been actively providing feedback on rules specifications.
Although the AMP/ASCO/CAP guidelines reduce interpretation discrepancy, subjective elements remain and require substantial clarification. The CVI, in collaboration with GA4GH VICC and the Cancer Genomics Consortium (CGC) participated in development of Standard Operating Procedures (SOP) for the classification of oncogenic variants (PMID:35101336). SC-VCEPs will utilize this SOP in curating SNVs or small deletions/insertions. Upcoming projects focus on evaluating somatic functional assays, standardizing somatic gene-disease curation and further developing the process to review and approve SC-VCEP specifications. Through the development of a SC-VCEP process, we aim to create greater consistency and accuracy of cancer variant interpretations for the improvement of patient care and genomic medicine.