With this macguffin’s loss, the thread of prophecy is severed. (Spoilers!)
YouTuber BOB_BestOfBugs, however, realized that there’s nothing stopping you from putting a Netherstone into a container like a crate or a sack (crucial to the Shadowboxing speedrun tech) and then getting rid of that container. I was able to replicate the trick in my own game, but curiously I only got the game over on losing my second Netherstone, so watch out for potentially soft locking yourself here.
What follows is the most luxurious sort of “you messed up, big time” scene you could possibly ask for, shades of firing a mining laser that wipes out all of humanity in System Shock and its remake.
(SPOILERS) YouTube Link
This also happens if you try to
spoiler
go back to the Underdark or mountain pass once Act 3 starts