Deletion-Insertion#
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.
Syntax#
Syntax | sequence_identifier ":r." position "delins" sequence |
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Examples |
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Explanation of Symbols | |
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Notes#
- all variants should be described at the DNA level, descriptions at the RNA and/or protein level may be given in addition.
- 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)).
- exception: two variants separated by one nucleotide, together affecting one amino acid, should be described as a "delins" (e.g.
- Adjoined transcripts from gene fusions 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..aggc
tou
cauu....aggc
.ga
cauu..r.775_777delinsc
: a deletion of nucleotides r.775 to r.777 ("uca", not described), replaced by nucleotides "c", changing..aggc
touca
uu....aggc
.c
uu..r.902_909delinsuuu
: a deletion of nucleotides r.902 to r.909, replaced by nucleotides uuur.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 asr.[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_004006.2r.415_1655delins[AC096506.5:g.409_1649]
: conversion replacing nucleotides r.414 to r.1655 with nucleotides 409 to 1649 as found in the genomic reference sequence AC096506.5r.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
- Adjoined transcripts from gene fusions (based on SVD-WG007)
- translocation-derived adjoined transcript:
NM_152263.2:r.-115_775::NM_002609.3:r.1580_*1924
describes an adjoined transcript from a TPM3::PDGFRB gene fusion, 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-derived adjoined transcripts:
NM_002354.2:r.-358_555::NM_000251.2:r.212_*279
: describes an adjoined transcript from an EPCAM::MSH2 gene fusion, 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 adjoined transcript from an EPCAM::MSH2 gene fusion, where only the fusion break point has been characterised, showing the insertion of a 17 nucletoide sequence (guaugauuuuuuaataa) between two adjoined transcripts
- translocation-derived adjoined transcript:
Discussion#
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 augu
to gc
caaugu
should be described as ug
car.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 cau
(a
acar.2077g>a
). In a patient I found the sequence cau
. Can I describe this variant as a
ua
acar.[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]
.