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Transcriptome analysis provides critical answers to the "variants of uncertain significance" conundrum.

ABSTRACT: 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.

SUBMITTER: Postel MD

PROVIDER: S-EPMC9560997 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Transcriptome analysis provides critical answers to the "variants of uncertain significance" conundrum.

Postel Mackenzie D MD Culver Julie O JO Ricker Charité C Craig David W DW

Human mutation 20220518 11

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 disparitie ...[more]

PMID: 35510381

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