RNA Recommendations

Deletion-insertion Variant

Definitions

Deletion-insertion (delins)
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. r.123_127delinsag

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

Note

  • all variants should be described at the DNA level, descriptions at the RNA and/or protein level may be given in addition.
  • prefix reference sequences accepted are r. (coding and non-coding RNA).
  • by definition, when one nucleotide is replaced by one other nucleotide the change is a substitution.
  • two variants separated by one or more nucleotides should preferably be described individually and not as a “delins”
    • exception: two variants separated by one nucleotide, together affecting one amino acid, should be described as a “delins” (e.g. r.142_144delinsugg p.(Arg48Trp)).
      NOTE: this prevents tools predicting the consequences of a variant to make conflicting and incorrect predictions of two different substitutions at one position
    • conversions, a sequence change where a range of nucleotides are replaced by a sequence from elsewhere in the genome, are described as a “delins”. The previous format “con” is no longer used (see Community Consultation SVD-WG009)).
  • RNA-fusion transcripts represent a special case of deletion-insertion variant. The fusion break point is described using ”::”
    NOTE: to avoid confusion, HGVS recommends to follow the HGNC guidelines to describe products of gene translocations or fusions (format GENESYMBOL1::GENESYMBOL2) and readthrough transcripts (format GENESYMBOL1-GENESYMBOL2)
  • for all descriptions the most 3’ position possible of the reference sequence is arbitrarily assigned to have been changed (3’rule)

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
  • r.142_144delinsugg (p.Arg48Trp)
    a deletion replacing nucleotides r.142 to r.144 (cga, not described) with ugg
    NOTE: the variant can also be described as r.[142c>u;144a>g], i.e. two substitutions. This format is preferred when either of the two variants is known as a frequently occurring variant (“polymorphism”)
  • RNA conversion (based on SVD-WG009)
    • NM_004006.2:r.2623_2803delins2804_2949
      conversion replacing nucleotides r.2623 to r.2803 (exon 21) with nucleotides r.2804 to r.2949 (exon 22) as found in the DMD coding RNA sequence file NM_004006.2
    • r.415_1655delins[AC096506.5:409_1649]
      conversion replacing nucleotides r.414 to r.1655 with nucleotides 409 to 1649 as found in the genomic reference sequence AC096506.5
    • r.1401_1446delins[NR_002570.3:r.1513_1558]
      conversion in exon 9 of the CYP2D6 gene replacing exon 9 nucleotides r.1401 to r.1446 with those of the 3’ flanking CYP2D7P1 gene, nucleotides r.1513 to r.1558
  • RNA fusion transcripts (based on SVD-WG007)
    • translocation fusion
      NM_152263.2:r.-115_775::NM_002609.3:r.1580_*1924 describes a TPM3::PDGFRB fusion transcript where nucleotides r.-115 to r.775 (reference transcript NM_152263.2, TPM3 gene) are coupled to nucleotides r.1580 to r.*1924 (reference transcript NM_002609.3, PDGFRB gene)
    • deletion fusion
      • NM_002354.2:r.-358_555::NM_000251.2:r.212_*279
        describes an EPCAM::MSH2 fusion transcript where nucleotides r.-358 to r.555 (reference transcript NM_002354.2, EPCAM gene) are coupled to nucleotides r.212 to r.*279 (reference transcript NM_000251.2, MSH2 gene)
      • NM_002354.2:r.?_555::guaugauuuuuuaataa::NM_000251.2:r.212_?
        describes an EPCAM::MSH2 fusion transcript where only the fusion break point has been characterised, showing the insertion of a 17 nucletoide sequence (guaugauuuuuuaataa) between two fusion transcripts

Q&A

What is an "indel"?

The term "indel" is not used in HGVS nomenclature (see Glossary). The term is confusing, having different meanings in different disciplines.

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].