Using multiplexed functional data to reduce variant classification inequities in underrepresented populations.

ABSTRACT:

Background

Multiplexed Assays of Variant Effects (MAVEs) can test all possible single variants in a gene of interest. The resulting saturation-style functional data may help resolve variant classification disparities between populations, especially for Variants of Uncertain Significance (VUS).

Methods

We analyzed clinical significance classifications in 213,663 individuals of European-like genetic ancestry versus 206,975 individuals of non-European-like genetic ancestry from All of Us and the Genome Aggregation Database. Then, we incorporated clinically calibrated MAVE data into the Clinical Genome Resource's Variant Curation Expert Panel rules to automate VUS reclassification for BRCA1, TP53, and PTEN.

Results

Using two orthogonal statistical approaches, we show a hi

SUBMITTER: Dawood M 

PROVIDER: S-EPMC11616159 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature