Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation

May Flowers; Alexa Dickson; Marcus J Miller; Elaine Spector; Gregory Mark Enns; Heather Baudet; Marzia Pasquali; Lemuel Racacho; Kianoush Sadre-Bazzaz; Ting Wen; Melissa Fogarty; Raquel Fernandez; Meredith A Weaver; Annette Feigenbaum; Brett H Graham; Rong Mao

doi:10.1016/j.ymgme.2023.107668

Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation

Mol Genet Metab. 2023 Nov;140(3):107668. doi: 10.1016/j.ymgme.2023.107668. Epub 2023 Jul 26.

Authors

May Flowers¹, Alexa Dickson², Marcus J Miller³, Elaine Spector⁴, Gregory Mark Enns⁵, Heather Baudet⁶, Marzia Pasquali⁷, Lemuel Racacho⁸, Kianoush Sadre-Bazzaz⁹, Ting Wen⁹, Melissa Fogarty⁹, Raquel Fernandez¹⁰, Meredith A Weaver¹⁰, Annette Feigenbaum¹¹, Brett H Graham³, Rong Mao¹²

Affiliations

¹ Invitae Corporation, San Francisco, CA 94103, USA.
² Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
³ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁴ Department of Pathology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Section of Clinical Genetics and Metabolism, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
⁵ Division of Medical Genetics, Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University, Stanford, CA 94304, USA.
⁶ Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
⁷ Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA; ARUP Laboratories, Salt Lake City, UT 84108, USA.
⁸ Department of Medical Genetics, Alberta Children's Hospital, Calgary, Alberta T3B6A8, Canada.
⁹ ARUP Laboratories, Salt Lake City, UT 84108, USA.
¹⁰ American College of Medical Genetics and Genomics, Bethesda, MD 20814, USA.
¹¹ Department of Pediatrics, Division of Genetics, Rady Children's Hospital and The University of California, San Diego, CA 92123, USA.
¹² Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA; ARUP Laboratories, Salt Lake City, UT 84108, USA. Electronic address: rong.mao@aruplab.com.

PMID: 37549443
PMCID: PMC10811274 (available on 2024-11-01)
DOI: 10.1016/j.ymgme.2023.107668

Abstract

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is a relatively common inborn error of metabolism, but due to difficulty in accurately predicting affected status through newborn screening, molecular confirmation of the causative variants by sequencing of the ACADVL gene is necessary. Although the ACMG/AMP guidelines have helped standardize variant classification, ACADVL variant classification remains disparate due to a phenotype that can be nonspecific, the possibility of variants that produce late-onset disease, and relatively high carrier frequency, amongst other challenges. Therefore, an ACADVL-specific variant curation expert panel (VCEP) was created to facilitate the specification of the ACMG/AMP guidelines for VLCADD. We expect these guidelines to help streamline, increase concordance, and expedite the classification of ACADVL variants.

Keywords: ACADVL; ClinGen; Pathogenicity; Variant interpretation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Acyl-CoA Dehydrogenase, Long-Chain / genetics
Congenital Bone Marrow Failure Syndromes / genetics
Genetic Testing
Genetic Variation
Humans
Infant, Newborn
Lipid Metabolism, Inborn Errors* / diagnosis
Lipid Metabolism, Inborn Errors* / genetics
Mitochondrial Diseases* / genetics
Muscular Diseases* / genetics

Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation

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