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Transcriptome analysis provides critical answers to the “variants of uncertain significance” conundrum
Author(s) -
Postel Mackenzie D.,
Culver Julie O.,
Ricker Charité,
Craig David W.
Publication year - 2022
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.24394
Subject(s) - biology , exome , transcriptome , genetics , exome sequencing , precision medicine , disease , genome , rna splicing , limiting , computational biology , bioinformatics , gene , rna , mutation , gene expression , medicine , mechanical engineering , pathology , engineering
While whole‐genome and exome sequencing have transformed our collective understanding of genetics' role in disease pathogenesis, there are certain conditions and populations for whom DNA‐level data fails to identify the underlying genetic etiology. Specifically, patients of non‐White race and non‐European ancestry are disproportionately affected by “variants of unknown/uncertain significance” (VUS), limiting the scope of precision medicine for minority patients and perpetuating health disparities. VUS often include deep intronic and splicing variants which are difficult to interpret from DNA data alone. RNA analysis can illuminate the consequences of VUS, thereby allowing for their reclassification as pathogenic versus benign. Here we review the critical role transcriptome analysis plays in clarifying VUS in both neoplastic and non‐neoplastic diseases.