Fig. 3: Detection of rare germline pathogenic in cancer patients using GATK-JG. | Genetics in Medicine

Fig. 3: Detection of rare germline pathogenic in cancer patients using GATK-JG.

From: Evaluating the molecular diagnostic yield of joint genotyping–based approach for detecting rare germline pathogenic and putative loss-of-function variants

Fig. 3

a confusion matrix of the quality class assignment of the pathogenic germline variants detected in 239 testicular cancer patients in the cancer-predisposition and ACMG gene sets (n = 151) in the presence and absence of the additional cancer-free cohort. b A total of 50 (92.6%) pathogenic variants were consistently detected by GATK-JG in the testicular cancer cohort (n = 239) while 4 (7.4%) clinically actionable pathogenic variants were detected by GATK-JG in only one or none of the computational runs despite being present in the raw genomic data file (c–f), highlighting a substantial limitation of the current standard germline variant detection method. g, h Conducting similar analyses on an independent cohort of 239 breast cancer patients showed that of 66 pathogenic variants in the raw variant callset, only 58 (87.9%, 95% CI: 77.5–94.6) pathogenic variants were considered “high-quality” by GATK-JG while 8 (12.1%, 95% CI: 5.4–22.5) variants went undetected by one or both computational runs. i–l Representative example of pathogenic cancer-risk variants that went undetected by one or both of GATK-JG runs.

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