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.
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
- 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)
- 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
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].