RNA Recommendations

Repeated sequences Variant

Definitions

Repeated sequence
a sequence where, compared to a reference sequence, a segment of one or more nucleotides (the repeat unit) is present several times, one after the other.

Description

Format (repeat position): “prefix”“position_repeat_unit””["”copy_number””]”, e.g. r.-125_-123[12]

  • “prefix” = reference sequence used = r.
  • “position_repeat_unit” = position (range) first repeat unit = -125_-123
  • [ = opening symbol for allele = [
  • “copy_number” = number of repeat copy = 12
  • ] = closing symbol for allele = ]

Format (sequence): “prefix”“position_repeat_start”“repeat_sequence””["”copy_number””]”, e.g. r.-125cug[12]

  • “prefix” = reference sequence used = r.
  • “position_repeat_start” = position first nucleotide repeat unit = -125
  • “repeat_sequence” = nucleotide sequence repeat unit = ggc
  • [ = opening symbol for allele = [
  • “copy_number” = number of repeat copy = 12
  • ] = closing symbol for allele = ]

Note

  • all variants should be described at the DNA level, descriptions at the RNA and/or protein level may be given in addition
  • reference sequences accepted are r. (coding and non-coding RNA).
  • repeated sequences include both small (mono-, di-, tri-, etc., nucleotide) and larger (kilobase-sized) repeats.
  • the format based on repeat position is preferred, descriptions of the repeat sequence quickly become too lengthy.
    • NOTE: while r.123cug[23] describes a repeat of 23 “cug” units, r.123_125[23] describes a tri-nucleotide repeat of 23 units which could be interrupted with other units (e.g. a rare “cua”). The description r.123cug[23] can thus only be used when the repeat was sequenced.
  • the format r.-125_-123cug[4], should not be used; it contains redundant information (“-125_-123” and “cug”).
  • for composite repeats the basic format can be used, successively listing each different repeat unit; r.456_465[4]466_489[9]490_499[3].

Examples

  • r.-124_-123[14] (alternatively r.-124ug[14])
    a repeated di-nucleotide sequence, with the first unit located from position r.-124 to r.-123, is present in 14 copies.
    NOTE: when the repeat is variable in the population and the reference sequence has 15 units, the description r.-123ug[14] is preferred over r.-97_-96del
    NOTE: when the repeat is variable in the population and the reference sequence has 15 units, the description r.-123ug[17] is preferred over r.-99_-96dup
  • r.-124_-123[14];[18] (alternatively r.-124ug[14];[18])
    a repeated di-nucleotide sequence, with the first unit located from position r.-124 to r.-123, is present in 14 copies on one allele and 18 copies on the other allele
  • FMR1 GGC-repeat
    in literature the Fragile-X tri-nucleotide repeat is known as the CGG-repeat. Hoever, based on a coding RNA reference sequence (GenBank NM_002024.5) and applying the 3’rule, the repeat has on the RNA level to be described as a “ggc”-repeat see Recommendations.
    • r.-128_-126[79]
      an extended repeat of exactly 79 units
      NOTE : r.-128ggc[79] can only be used when the repeat has been sequenced, excluding it is interrupted by one or more “gga”-triplets
    • r.-128_-126[(600_800)]
      the repeated tri-nucleotide sequence, starting at position c.-128, has an estimated size of between 600 to 800 copies.
      NOTE: the repeat can be pure or a mix of “ggc” and “gga” triplets.
  • HD AGC-repeat
    based on the HTT (huntingtin) coding DNA reference sequence (GenBank NM_002111.6), applying the 3’rule, the Huntington’s Disease tri-nucleotide repeat is described as an AGC (not CAG) repeat.
    • c.53AGC[19]
      NOTE: the coding RNA reference sequence (NM_002111.6) contains an allele of 21 “agc” repeats
      NOTE: on protein level the reference allele contains 21 Gln’s, described as p.Gln[21] (alternatively p.Q[21]). The difference derives from the fact that the “agc” repeat is interrupted by a “aac”-triplet (“caa” coding) at position 20.
    • r.53_55[31]
      the coding RNA reference sequence (NM_002111.6) contains a tri-nucleotide allele of 32 repeats (agc-19, aac, agc, cgc, cac, cgc-7, cuc-2) encoding 21 Gln and 11 Pro-residues.