how can a DELETION be not a NULL variant?

Question

[cocchi.e89]

I've found a var (exam, human) in ROBO2 gene: 3-77684075-ACAG-A According to Varsome this is not a NULL variant. Sorry if it sounds silly, but how can a DELETION not being a NULL variant?

Thanks a lot in advance for any help!

[Pierre Lindenbaum]

I cannot find the word "NULL" in the page...

[cocchi.e89]

In the ACMG classification, PVS1 explanation: "Not a null variant."

Answer 1

[Jean-Karim Heriche]

In genetics, null refers to a complete loss of function. A deletion could be considered not a null if it doesn't abolish completely the function of the gene. For example, deletion of an intronic sequence may have no detectable functional effect or deletion of the C-terminal end of a protein may only partially impair its function.

[rbagnall]

Precisely! In this case it is a deletion of 3 base pairs in the coding region of ROBO2 (ACAG goes to A by loss of CAG). Therefore it is an 'in-frame' deletion, which causes the protein to be shortened by one amino acid residue.