can I create a transparent cutout in one video source layer?

[Xylem]

I am recording live lectures for online learning. Video cam source is the base layer showing me lecturing by a projection screen and pointing out details in power point lecture.
Layer 2 is a screen capture of the desk top, sized so that the Power point slides exactly match the size on the projection screen (slide in slide). That part is easy enough.
But, when my hand or pointer moves over the slide boundary it vanishes under the screen capture overlay. I had in mind to duplicate the base layer on top and figure out a way to cut out the projection screen part so that my hand or pointer would now be on top of the screen capture layer and would be visible.
Any ideas about how I could create that cutout part to make the top layer transparent within the cutout box area? Is it even possible?

 

[AskMP]

You should be able to do this with a difference matte but there will likely be variances, time delays and artifacts if the videos are not perfectly matching (pulling video from a camera vs raw feed will be slightly different). Essentially, you'd be looking to do what many of the current background replacement features of conference call software has been doing but applying it to a small section of the screen and using an alternative shot for the source.

Honestly speaking here, you shouldn't be pointing to the board with your hand. Use a pointing device on the computer. If you're presenting the same output that your capturing, a digital stylus, radial highlight or colour overlay would likely be better for both your online audience AND your in-person. Think of sports highlighers, sure they have started doing it in front of a display, but they use a touch display and draw on their thoughts. They don't just point it out.

That being said, there is definitely a market for your original suggestion, it's more that I believe you're description of the need has better solutions.