A germline pathogenic variant identified in a pediatric high-grade glioma.

(partner and localizer of BRCA2) gene encodes a protein that colocalizes with in nuclear foci and likely permits the stable intranuclear localization and accumulation of plays a critical role in maintaining genome integrity through its role in the Fanconi anemia and homologous recombination DNA repair pathways. It has a known loss-of-function disease mechanism. Biallelic pathogenic variants have been described in autosomal recessive Fanconi anemia. Heterozygous pathogenic variants in are associated with increased risk for female and male breast cancer and pancreatic cancer ( 324: 217; 71: 2222-2229; 371: 497-506). Heterozygous germline mutations have also been observed in patients with medulloblastoma ( 19: 785-798). However, -related cancer predisposition to high-grade gliomas has not been reported. Here we report a germline pathogenic variant (c.509_510delGA, p.Arg170Ilefs*14, NM_024675.3) found in a pediatric patient with high-grade glioma. This variant was first identified by tumor sequencing using the Children's Hospital of Philadelphia (CHOP) Comprehensive Solid Tumor Panel and then confirmed to be a germline change using the CHOP Comprehensive Hereditary Cancer Panel on DNA from a blood sample of this patient. Parental studies showed that this variant was paternally inherited. Further studies are needed to illustrate if pathogenic variants in convey increased risk to developing brain tumor. This case also highlights the potential of identifying germline mutation through tumor sequencing.