Targeted tumor only sequencing has become a standard practice in cancer diagnostics. This study aims to develop an approach for robust copy number variant (CNV) calling in tumor samples using only off-target region (OTR) reads. We also established a clinical use case for HRD score estimation (HRDest) using the sum of tumor allelic imbalance (TAI) and large-scale state transitions (LST) scores without the need for loss of heterozygosity (LOH) information. We demonstrated a strong correlation between HRD score and the sum of TAI + LST in the TCGA cohort (R=0.99, p= 2.2e-16) and in a clinical in-house cohort of 34 tumors (R=0.9, p=5.1e-13) comparing WES and targeted sequencing data. We compared HRDest scores from 1009 real world cases with the TCGA dataset and showed that there were no significant differences in HRD score distribution within the analyzed tumor types. As a control, commercially available HRD standards were also sequenced and the HRDest scores obtained from the OTR reads were well within the HRD reference range provided by the manufacturer. In conclusion, we showed that OTR reads of tumor-only panel sequencing can be used to determine genome-wide CNV profiles and to approximate HRD scores.