Introduction:
Germline genetic testing can reveal variants that are pathogenic,
benign, or of uncertain significance (VUS). Reference genome databases
used to assign pathogenicity are largely composed of data from patients
of European ancestry and significantly lack input from the remainder of
the world population (Fig. 1)1. Over 86% of all
participants in genome-wide association studies (GWAS) in 2023 are of
European ancestry, and only 1% are of African or Hispanic ancestry.
Patients of underrepresented descent are more likely to carry VUS than
white patients, which may be explained by their relative absence from
these databases2–4. Inequitable representation may
impact the care of many of these patients. We describe seven pediatric
hematology/oncology patients recently seen in our pediatric
hematology-oncology clinic located in Bronx County, New York City, where
only 8.7% of the community identifies as white5.
Unusual clinical findings prompted germline genetic testing that
identified VUS or novel pathogenic variants in clinically relevant
genes, prompting alterations in treatment and outcomes.