question concerning implementation HGVS 3´ rule of variants

[Katrien De Mulder]

Dear,

We are currently using transvar as annotator in our pipeline.
We are really satisfied with the software.

However, we have a question concerning the support of both left-alignment and right-alignment convention in reporting indels and duplications.

In a recent EQC-program, we identified a deletion in the EGFR gene as follows:
c.2240_2257del <-> HGVS c.2237_2257delinsTAT
p.(Leu747_Pro753delinsSer) <-> HGVS p.(Glu746_Pro753delinsValSer)

Following the HGVS guidelines, a 3’ rule for alignment is prefered. When reading the TRANSVAR manual, we believe reporting the correct variant is possible with transvar as it supports both left-alignment and right-alignment convention.

On p15 of the transvar manual (2.5.4 release), an example is shown in which a difference between left and right-aligned identifiers is shown. I now have 3 questions

• Is the term ‘unalign_cDNA´ used for right_align_cDNA? I only see left_align_cDNA in the examples of the manual?
• If we look in our raw data for this specific deletion mentioned above, there is no difference between the left_align_cDNA and unalign_cDNA description
  left_align_gDNA=g.55242470_55242487del18;unaligned_gDNA=g.55242470_55242487del18;left_align_cDNA=c.2240_2257del18;unalign_cDNA=c.2240_2257del18;dbxref=GeneID:1956,HGNC:3236,HPRD:00579,MIM:131550;aliases=NP_005219;source=RefSeq
• Might this issue be solved if we upgrade from 2.4.1 to 2.5.4 version of the software or is there another option we have to include in the code?

Looking forward hearing from you,
Thanks in advance,

Kind regards,
Katrien