Comment 8 for bug 47379

Here's a reference with some relevance for the present report.

https://live.gnome.org/NetworkManager/SystemSettings#ifupdown

"The ifupdown plugin also uses [...] NetworkManager.conf (0.8.1 and later) for some configuration. All ifupdown-specific options go in a "[ifupdown]" section. If the "managed" key is set to "false", then any device listed in /etc/network/interfaces will be completely ignored by NetworkManager. Remember that NetworkManager controls the default route, so because the device is hidden, NetworkManager will assign the default route to some other device."