I was playing all of a sudden all of the fighting skills wouldn’t respond either by mouse or keyboard…I was still able to move my character around but fight Uh Uh 
Yeah it is happening to a lot of other people. There are other threads about it:
https://us.forums.blizzard.com/en/d4/t/skills-not-working/24545
Leaving the game and going back in fixes it.
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PS I also saw a lot of lag and freezing issues…Nope not good in a game that cost from $70.00 to Over $100.00! Jay Wilson and his Dev’s should have stayed in World of Warcrap where supposedly they knew what they were doing! They’ve managed to !
Up every Diablo they’ve been involved in! And don’t say they did OK on D2R because they didn’t work that they contracted that out to someone ELSE!