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Table 4 Clinically impactful germline mutations

From: Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations

PIP ID Diagnosis Alteration Mutation Change Mutation type Clinical utility Implication Previously known or suspected
Hematologic conditions
 14-19751 HLH MLL2 c.11640_11640delG; c.15631G > A p.M3881Cfs*9 (de novo); p.E5211K Compound heterozygous, frameshift Diagnostic Kabuki syndrome; Transplantation withheld No
 15-90485 HLH C1QA c.622C > T p.Gln208Ter Homozygous, nonsense Diagnostic C1Q deficiency No
 15-33031 MDS GATA2 (de novo) c.16delG p.(E6fs) Heterozygous, frameshift Supports transplant recommendation; Genetic counseling for family Increased risk for developing AML and MDS No
 14-92247 ALL PMS2 c.1376C > G p.S459X Homozygous, missense Diagnostic; Health maintenance/ Genetic counseling Constitutional mismatch repair deficiency syndrome; Lynch syndrome (parents) No
 15-46877 HLH XIAP c.1328G > C p.R443P Missense Diagnostic X-linked lymphoproliferative syndrome 2 (XLP2); Transplantation recommended No
 14-19750 AML RUNX1 c.806-2A > G r.Spl? Heterozygous splice site Diagnostic Familial platelet disorder; Transplantation donor changed from sibling to unrelated donor No
Solid tumors
 14-56374 Hepatoblastoma APC c.3340C > T p.R1114 Nonsense Diagnostic; Health maintenance/ Genetic counseling Familial adenomatous polyposis Yes
 15-33544 Poorly differentiated carcinoma with focal neuroendocrine differentiation APC (de novo) c.4660_4661insA p.E1554fs Frameshift Diagnostic; Health maintenance/ Genetic counseling Gardner syndrome; Familial adenomatous polyposis No
 15-35162 Osteosarcoma RB1 c.1216-3A > G p.? Splice site Health maintenance/ Genetic counseling Increased risk for developing other cancers Yes
 15-44470 Medulloblastoma ATM c.566G > A; c.8266A > T p.R189K; p.K2756* Missense, nonsense Health maintenance/ Genetic counseling Increased risk for developing other cancers No
 15-78886a Pineoblastoma UGT1A1 *28 allele (“(TA)7TAA”)   Homozygous Pharmacogenomic Drug sensitivity No
 15-78886a Pineoblastoma DICER1 c.4807dupC p.L1603Pfs Frameshift Health maintenance/ Genetic counseling Risk of ovarian Sertoli-Leydig cell tumor No
 15-17264 Hepatocellular carcinoma UGT1A1 *28 allele   Heterozygous Pharmacogenomic Drug sensitivity No
ACMG secondary findings
 15-29224 AML TP53 c. 644G > A p.S215N Missense Affects therapy; Health maintenance/ Genetic counseling Explains lack of response to conventional therapy; Increased risk for developing other cancers No
 14-59462 Nested stromal epithelial tumor of the liver BRCA1 c.68._69delAG p.Glu23Valfs Frameshift Health maintenance/ Genetic counseling Breast cancer No
 16-88073 Ependymoma BRCA1 c.5587_5594delGTAGCACT p.V1863Lfs*35 Frameshift Health maintenance/ Genetic counseling Breast cancer No
 14-75899 Neuroblastoma RYR1 c.6838G > A p.V2280I Missense Health maintenance/ Genetic counseling Malignant hyperthermia No
 14-13487 Osteosarcoma TNNT2 c.422G > A p.Arg141Gln Heterozygous Health maintenance/ Genetic counseling Dilated cardiomyopathy No
 15-34296 Ependymoma VHL c.539 T > C p.I180T Missense Health maintenance/ Genetic counseling Von Hippel Lindau syndrome No
  1. aSame patient
  2. ALL acute lymphoblastic leukemia, AMKL acute megakaryoblastic leukemia, AML acute myeloid leukemia, HLH hemophagocytic lymphohistiocytosis, JMML juvenile myelomonocytic leukemia