Failure to Detect Mutations in U2AF1 due to Changes in the GRCh38 Reference Sequence.
2022 Mar
Journal Article
Authors:
Miller, C.A.;
Walker, J.R.;
Jensen, T.L.;
Hooper, W.F.;
Fulton, R.S.;
Painter, J.S.;
Sekeres, M.A.;
Ley, T.J.;
Spencer, D.H.;
Goll, J.B.;
Walter, M.J.
Secondary:
J Mol Diagn
Volume:
24
Pagination:
219-223
Issue:
3
PMID:
35041928
URL:
https://pubmed.ncbi.nlm.nih.gov/35041928/
DOI:
10.1016/j.jmoldx.2021.10.013
Keywords:
Humans; Leukemia, Myeloid, Acute; Mutation; Splicing Factor U2AF
Abstract:
The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. This study describes the problem in detail and shows that a modified GRCh38 reference build with unchanged coordinates can be used to ameliorate the issue.
