RNA Recommendations

Deletion/ insertion (indel) Variant


Definitions

Deletion-insertion (indel)
a sequence change where, compared to a reference sequence, one or more nucleotides are replaced by one or more other nucleotides and which is not a substitution, inversion or conversion.

Description

Format: “prefix”“position(s)_deleted”“delins”“inserted_sequence”, e.g. g.123_127delinsAG

“prefix” = reference sequence used = g.
“position(s)_deleted” = position nucleotide or range of nucleotides deleted = 123_127
“delins” = type of change is a deletion-insertion (indel) = delins
“inserted_sequence” = description inserted sequence = AG


Note

  • prefix reference sequences accepted are g., m., c. and n. (genomic, mitochondrial, coding DNA and non-coding DNA).
  • by definition, when one nucleotide is replaced by one other nucleotide the change is a substitution.
  • for all descriptions the most 3’ position possible of the reference sequence is arbitrarily assigned to have been changed (3’rule)
    • the 3’rule also applies for changes in single residue stretches and tandem repeats (nucleotide or amino acid)
    • the 3’rule applies to ALL descriptions (genome, gene, transcript and protein) of a given variant
  • under discussion, see Proposal for complex variants
    { } (curly braces) can be used to list any change in the inserted sequence (“inserted_sequence”) which is different when compared to the source, e.g. g.123_345delins1101_1222{1167A>G}

Examples

  • r.775delinsga
    a deletion of nucleotide r.775 (a “u”, not described), replaced by nucleotides “ga”, changing ..aggcucauu.. to ..aggcgacauu..
  • r.775_777delinsc
    a deletion of nucleotides r.775 to r.777 (“uca”, not described), replaced by nucleotides “c”, changing ..aggcucauu.. to ..aggccuu..
  • r.902_909delinsuuu
    a deletion of nucleotides r.902 to r.909, replaced by nucleotides uuu

Q&A

What is an "indel"?

An "indel", deletion/insertion in HGVS nomenclature, is a variant which is a combination of a deletion and an insertion. Based on existing nomeclature, the variant can be described as a deletion and insertion occuring at the same position, using the format r.112_117delinsug.

Can I describe a "gc" to "ug" variant as a dinucleotide substitution (r.4gc>ug)?

No this is not allowed. By definition a substitution changes one nucleotide into one other nucleotide (see Substitution). The change "augugcca" to 'auguugca" should be described as r.5_6delinsug, i.e. a deletion/insertion (indel).

The BRCA1 coding RNA reference sequence from position r.2074 to r.2080 is ..caugaca.. A variant frequently found in the population is ..cauaaca.. (r.2077g>a). In a patient I found the sequence ..caua uaaca.. Can I describe this variant as r.[2077g>a;2077_2078insua]?

The shortest description of this variant is r.2077delinsaua. However, since the variant is likely a combination of two other variants it is acceptable to describe it as r.[2077g>a;2077_2078insua].