Manta is a novel method for rapid detection of structural variants (SVs) and indels in next-generation sequencing data, optimized for germline and somatic analysis. It can identify SVs, medium-sized indels, and large insertions on standard compute hardware in less than a tenth of the time required by comparable methods. Manta uses an efficient parallel workflow to discover variants from paired and split-read mapping information. It provides scoring models for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs. Manta consistently assembles a higher fraction of calls to base-pair resolution, improving downstream annotation and clinical significance analysis. The method is released under the open-source GPLv3 license and is available from the Illumina GitHub repository. Manta has been evaluated against other tools, demonstrating high variant call quality with significantly reduced compute costs.Manta is a novel method for rapid detection of structural variants (SVs) and indels in next-generation sequencing data, optimized for germline and somatic analysis. It can identify SVs, medium-sized indels, and large insertions on standard compute hardware in less than a tenth of the time required by comparable methods. Manta uses an efficient parallel workflow to discover variants from paired and split-read mapping information. It provides scoring models for germline analysis of diploid individuals and somatic analysis of tumor-normal sample pairs. Manta consistently assembles a higher fraction of calls to base-pair resolution, improving downstream annotation and clinical significance analysis. The method is released under the open-source GPLv3 license and is available from the Illumina GitHub repository. Manta has been evaluated against other tools, demonstrating high variant call quality with significantly reduced compute costs.