Mouse clicks unresponsive in-game

I've played games, but this time I started it in windowed mode and didn't go full screen. The mouse cursor is visible and remains confined as it should, and I am able to use keyboard shortcuts, but left or right-clicking has no effect. For example, I could select my hero (with F1) and press D to activate her ability (I was playing the chaos hero), and see the circle showing the AoE, move the targeting line with my mouse, but not activate it. I haven't run into this before, I'll try to get more info on what circumstances caused it.

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