Learn Russian: Мы знаем, что начальника нет в офисе. - We know that the boss is not in the office.

This is the Genitive case, which is required after the word нет (meaning "is not present" or "there is no"). Since начальник is a masculine noun ending in a consonant, we add -а to the end to show that he is the one who isn't there.

Doesn't нет just mean "no"? How does it mean "is not" in this sentence?

You're right that нет usually means "no" when answering a question. However, it also acts as a special word for absence, meaning "is not present" or "there is no". In Russian, you don't use the verb "to be" plus "not" to say someone is absent; you just use нет followed by the person or thing in the Genitive case.

Why is there a comma right before что?

In Russian punctuation, you must put a comma before the conjunction что (that) when it connects two halves of a sentence. English often drops the comma or even the word "that" entirely (like "We know the boss is not..."), but Russian strictly requires both the comma and the word что.

Just to review, why does офис change to в офисе?

This is the Prepositional case in action! Because we are talking about a location (where the boss is not), we use the preposition в (in) and add an -е to the end of the regular masculine noun офис.