Imperial College London

Dr Nicky Whiffin

Faculty of MedicineNational Heart & Lung Institute








Hammersmith HospitalHammersmith Campus






BibTex format

author = {Wang, Q and Pierce-Hoffman, E and Cummings, BB and Alföldi, J and Francioli, LC and Gauthier, LD and Hill, AJ and O'Donnell-Luria, AH and Genome, Aggregation Database Production Team and Genome, Aggregation Database Consortium and Karczewski, KJ and MacArthur, DG},
doi = {10.1038/s41467-019-12438-5},
journal = {Nat Commun},
title = {Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes.},
url = {},
volume = {11},
year = {2020}

RIS format (EndNote, RefMan)

AB - Multi-nucleotide variants (MNVs), defined as two or more nearby variants existing on the same haplotype in an individual, are a clinically and biologically important class of genetic variation. However, existing tools typically do not accurately classify MNVs, and understanding of their mutational origins remains limited. Here, we systematically survey MNVs in 125,748 whole exomes and 15,708 whole genomes from the Genome Aggregation Database (gnomAD). We identify 1,792,248 MNVs across the genome with constituent variants falling within 2 bp distance of one another, including 18,756 variants with a novel combined effect on protein sequence. Finally, we estimate the relative impact of known mutational mechanisms - CpG deamination, replication error by polymerase zeta, and polymerase slippage at repeat junctions - on the generation of MNVs. Our results demonstrate the value of haplotype-aware variant annotation, and refine our understanding of genome-wide mutational mechanisms of MNVs.
AU - Wang,Q
AU - Pierce-Hoffman,E
AU - Cummings,BB
AU - Alföldi,J
AU - Francioli,LC
AU - Gauthier,LD
AU - Hill,AJ
AU - O'Donnell-Luria,AH
AU - Genome,Aggregation Database Production Team
AU - Genome,Aggregation Database Consortium
AU - Karczewski,KJ
AU - MacArthur,DG
DO - 10.1038/s41467-019-12438-5
PY - 2020///
TI - Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes.
T2 - Nat Commun
UR -
UR -
UR -
VL - 11
ER -