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. 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
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.
two variants separated by one or more nucleotides should preferably be described individually and not as a “delins”
two variants separated by one nucleotide, together affecting one amino acid, should be described as a “delins” (e.g. c.142_144delinsTGG (p.Arg48Trp)).
NOTE: this prevents tools predicting the consequences of a variant to make erroneous predictions based on e.g. two individual substitutions
for all descriptions the most 3’ position possible of the reference sequence is arbitrarily assigned to have been changed (3’rule)
a deletion of nucleotide g.6775 (a T, not described), replaced by nucleotides GA, changing ..AGGCTCATT.. to ..AGGCGACATT..
a deletion of nucleotides g.6775 to g.6777 (TCA, not described), replaced by nucleotides C, changing ..AGGCTCATT.. to ..AGGCCTT..
a deletion replacing nucleotides c.142 to c.144 (CGA, not described) with TGG
NOTE: the variant can also be described as c.[142C>T;144A>G], i.e. two substitutions. This format is preferred when either of the two variants is known as a frequently occurring variant (“polymorphism”).
a deletion of nucleotides g.9002 to g.9009, replaced by nucleotides TTT
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 nomenclature, 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).
Are there specific recommendations regarding the maximum number of unchanged nucleotides between two single nucleotide variants and whether the change is described as a "delins" or as two separate changes?
Yes, two variants separated by one or more nucleotides should preferably be described individually and not as a "delins" (unless they together affect one amino acid). Why? First, the two variants may have been reported (or might occur) individually. Second, sequence analysis pipelines will describe such variants individually, giving the problem that an overlap with the description of the combined variant ("delins" description) might be missed in the annotation step (database queries).
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 better to describe it as c.[2077G>A;2077_2078insTA].