Open for comments - SVD-WG003
Published: May 14, 2015
Closes: July 16, 2015
SVD-WG003 suggests to extend the current HGVS recommendations for the
description of sequence variants with the proposal below. Comments can be
sent to the HGVS/HVP/HUGO Sequence Variant Description Working Group
(SVD-WG), addressed to "Varnomen
@ variome.org", Subject:
SVD-WG003. Comments need to be sent ultimately
July 16, 2015).
Exon del/dup descriptions
Deletions (duplications) detected by
MLPA tests (testing all exons) should be described using the format
format suggested originally to describe deletions/duplications detected by
MLPA tests (testing all exons) is like c.650-?_1331+?del, i.e. a deletion
starting in the intron preceding c.650 (first nucleotide of the first
deleted exon) and ending in the intron after c.1331 (last nucleotide of the
last deleted exon). This format conflicts
with the basic format to describe deletions/duplications where the
break point was not sequenced but where a region of uncertainty is present
This format is (last-normal_first-changed)_(last-changed_first-normal). The
Committee considered the format c.(649_650)_(1331_1332)del which is shorter
but not specifically indicates that the expected break points of the change
are in an intron.
be 100% accurate one should not use the position of the introns in the
description of the change but the location of the probes actually tested in
the assay. The current proposal bears in mind that: i) it is not
straightforward what probe position to use (see Uncertainties),
ii) the additional detail would hardly add useful information, and iii) we
should preferably not deviate too far from the original proposal (i.e. to
use flanking intron locations). When one wants to use probe locations (e.g.
with breakpoints in large exons) the suggestion is to use the central
position of the probes in variant descriptions.
- c.(649+1_650-1)_(1331+1_1332-1)del describes a deletion of exons
8 to 11 (DMD gene) with breakpoints in the introns between nucleotides
c.649 and c.650 (intron 7) on one side and nucleotides c.1331 and c.1332
(intron 11) on the other side. The flanking exons (7 and 12) on either
side were tested and found not deleted.
c.(649+1_650-1)_(1331+1_1332-1)dup describes a duplication of the same
- c.(516+1_517-1)_(1970_6774)del describes a deletion in the BRCA2
gene with one break point in the intron between nucleotides c.516 and
c.517 (intron 6) and one breakpoint in exon 10 between nucleotides
c.1970 and c.6774. Flanking exons (5 and 11) on each side were tested
and found not deleted. Description of the break point in exon 10 was
derived from the two MLPA probes tested, taken the central nucleotide
position per probe.
c.(516+1_517-1)_(1970_6774)dup describes a duplication of the same
the description "dup"
may by definition
only be used when the additional copy is located directly 3'-flanking the
original copy (a tandem duplication). In most cases there will be no
experimental proof, one simply detects the presence of an additional copy
that in theory can be anywhere in the genome (inserted / transposed).
Discussions are ongoing how to include this uncertainty best in the
description: a proposal will follow later.
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