Discrepancies in Indel Nomenclature
Due to different nomenclature guidelines (left versus right justification), a deletion or insertion Canonical Allele may have multiple contextual allele expressions on a single reference sequence. For example, the deltaF508 variant in CFTR is the most common CF-causing variant. This variant results in an inframe deletion of a phenylalanine (Phe/F) at position p.508.
| Reference | Coorindates | Deleted Nucleotides |
|---|---|---|
| NC_000007.13 (GRCh37) | g.117199645_117199647delTCT | TCT |
| NC_000007.14 (GRCh38) | g.117559591_117559593delTCT | TCT |
| NC_000007.13 (GRCh37) | g.117199646_117199648delCTT | CTT |
| NC_000007.14 (GRCh38) | g.117559592_117559594delCTT | CTT |
| NM_000492.3 | c.1520_1522delTCT | TCT |
| NM_000492.3 | c.1521_1523delCTT | CTT |
| NP_000483.3 | p.Phe508del |
Although this Canonical Allele has multiple expressions on the same reference (such as c.1520_1522delTCT and c.1521_1523delCTT), all describe the same Canonical Allele.
Deletions with varying impact size depending on reference
| Reference | Coorindates | # of Deleted Nucleotides | |— |— |— |— |— | | NC_000010.10 (GRCh37) | g.50701279_50708585del | 7306 | | NM_000124.2 | c.1684_1705del | 21 |
Based on the mRNA coordinates, this variant results in a deletion of 21 nucleotides with a predicted frameshift impact: p.Arg562LeufsX2. However, in actuality, this deletion spans an intron resulting in 7306 deleted nucleotides.