DNA 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

  • g.6775delinsGA
    a deletion of nucleotide g.6775 (a T, not described), replaced by nucleotides GA, changing ..AGGCTCATT.. to ..AGGCGACATT..
  • g.6775_6777delinsC
    a deletion of nucleotides g.6775 to g.6777 (TCA, not described), replaced by nucleotides C, changing ..AGGCTCATT.. to ..AGGCCTT..
  • c.145_147delinsTGG
    a deletion replacing nucleotides c.145 to c.147 (CGA, not described) with TGG
    NOTE: the variant can also be described as c.[145C>T;147A>G], i.e. two substitutions. This format is preferred when either of the two variants is known as a frequently occurring variant (“polymorphism”).
  • g.9002_9009delinsTTT
    a deletion of nucleotides g.9002 to g.9009, replaced by nucleotides TTT

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 g.112_117delinsTG.

Can I describe a GC to TG variant as a dinucleotide substitution (g.4GC>TG)?

No this is not allowed. By definition a substitution changes one nucleotide into one other nucleotide (see Substitution). The change TGTGCCA to TGTTGCA should be described as g.4_5delinsTG, i.e. a deletion/insertion (indel).

The BRCA1 coding DNA reference sequence from position c.2074 to c.2080 is ..CATGACA.. A variant frequently found in the population is ..CATAACA.. (c.2077G>A). In a patient I found the sequence ..CATA TAACA.. Can I describe this variant as c.[2077G>A;2077_2078insTA]?

The shortest description of this variant is c.2077delinsATA. However, since the variant is likely a combination of two other variants it is acceptable to describe it as c.[2077G>A;2077_2078insTA].