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, can be described as a “delins” (e.g. r.142_144delinsugg (p.Arg48Trp))
for all descriptions the most 3’ position possible of the reference sequence is arbitrarily assigned to have been
a deletion of nucleotide r.775 (a “u”, not described), replaced by nucleotides “ga”, changing ..aggcucauu.. to ..aggcgacauu..
a deletion of nucleotides r.775 to r.777 (“uca”, not described), replaced by nucleotides “c”, changing ..aggcucauu.. to ..aggccuu..
a deletion of nucleotides r.902 to r.909, replaced by nucleotides uuu
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”)
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 r.112_117delinsug.
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].