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Importance of adopting standardized MANE transcripts in clinical reporting

  • Caroline F. Wright
    Affiliations
    Institute of Biomedical and Clinical Science, University of Exeter Medical School, Royal Devon and Exeter Hospital, Exeter, United Kingdom
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  • David R. FitzPatrick
    Affiliations
    MRC Human Genetics Unit, Institute of Genetic and Cancer, The University of Edinburgh, Edinburgh, United Kingdom
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  • James S. Ware
    Affiliations
    National Heart and Lung Institute and MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom
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  • Heidi L. Rehm
    Correspondence
    Correspondence and requests for materials should be addressed to Heidi L. Rehm, Center for Genomic Medicine, Massachusetts General Hospital, Simches Research Building, CPZN-5-812, 185 Cambridge Street, Boston, MA 02114
    Affiliations
    Center for Genomic Medicine, Massachusetts General Hospital and Broad Institute of MIT and Harvard, Boston, MA
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  • Helen V. Firth
    Correspondence
    Helen V. Firth, Department of Medical Genetics, Addenbrooke’s Hospital, Cambridge University Hospitals, Box 134, Cambridge CB2 0QQ, United Kingdom.
    Affiliations
    East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom

    Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
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Published:November 28, 2022DOI:https://doi.org/10.1016/j.gim.2022.10.013
      Why use MANE Select and MANE Plus Clinical?
      • MANE Select provides a single default transcript per gene agreed internationally.
      • MANE Plus Clinical provides additional transcripts for use in a subset of genes in which more than one transcript is known to be clinically important (eg, tissue-specific transcripts).
      • Transcripts are selected on the basis of the strongest available biological evidence.
      • The transcripts in these data sets have 1:1 correlation with the GRCh38 human reference genome sequence.
      • These data sets facilitate accurate and unambiguous reporting and communication between clinicians, scientists and patients.

      GenePod

      December 2, 2022

      December 2022: Standardizing variant annotation

      One of the challenges in the attempt to standardize variant research, and understand whether a new variant is benign or pathogenic, arises from the fact that the human genome has largely been annotated by two major groups, and they have two different datasets of transcripts: The NCBI, which is based largely in the US, produced the RefSeq database of transcripts, and the EMBL-EBI in Europe produced the Ensembl/GENCODE set of transcripts. In April 2022, a team of researchers introduced the MANE project, or The Matched Annotation from the NCBI and EMBL-EBI , as an attempt to harmonize gene and transcript annotation. While online genome browsers quickly made the change to MANE, not everyone has yet made the switch, as addressed in a recent commentary in Genetics in Medicine. One of the commentary’s authors, Caroline Wright, PhD, professor of genomic medicine at the University of Exeter, joined GenePod to discuss the importance of MANE and its path forward.

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      References

        • Morales J.
        • Pujar S.
        • Loveland J.E.
        • et al.
        A joint NCBI and EMBL-EBI transcript set for clinical genomics and research.
        Nature. 2022; 604: 310-315https://doi.org/10.1038/s41586-022-04558-8
        • Frankish A.
        • Diekhans M.
        • Jungreis I.
        • et al.
        GENCODE 2021.
        Nucleic Acids Res. 2021; 49: D916-D923https://doi.org/10.1093/nar/gkaa1087
        • O’Leary N.A.
        • Wright M.W.
        • Brister J.R.
        • et al.
        Reference sequence (RefSeq) database at NCBI: current status, taxonomic expansion, and functional annotation.
        Nucleic Acids Res. 2016; 44: D733-D745https://doi.org/10.1093/nar/gkv1189
        • Gudmundsson S.
        • Singer-Berk M.
        • Watts N.A.
        • et al.
        Variant interpretation using population databases: lessons from gnomAD.
        Hum Mutat. 2022; 43: 1012-1030https://doi.org/10.1002/humu.24309
        • den Dunnen J.T.
        • Dalgleish R.
        • Maglott D.R.
        • et al.
        HGVS recommendations for the description of sequence variants: 2016 update.
        Hum Mutat. 2016; 37: 564-569https://doi.org/10.1002/humu.22981
        • Landrum M.J.
        • Lee J.M.
        • Benson M.
        • et al.
        ClinVar: public archive of interpretations of clinically relevant variants.
        Nucleic Acids Res. 2016; 44: D862-D868https://doi.org/10.1093/nar/gkv1222
        • Foreman J.
        • Brent S.
        • Perrett D.
        • et al.
        DECIPHER: supporting the interpretation and sharing of rare disease phenotype-linked variant data to advance diagnosis and research.
        Hum Mutat. 2022; 43: 682-697https://doi.org/10.1002/humu.24340
        • van Spronsen F.J.
        • Blau N.
        • Harding C.
        • Burlina A.
        • Longo N.
        • Bosch A.M.
        Phenylketonuria.
        Nat Rev Dis Primers. 2021; 7: 36https://doi.org/10.1038/s41572-021-00267-0
        • Di Iorio V.
        • Karali M.
        • Melillo P.
        • et al.
        Spectrum of disease severity in patients with X-linked retinitis pigmentosa due to RPGR mutations.
        Invest Ophthalmol Vis Sci. 2020; 61: 36https://doi.org/10.1167/iovs.61.14.36
        • Epilepsy Genetics Initiative
        De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy.
        Genet Med. 2018; 20: 275-281https://doi.org/10.1038/gim.2017.100