Batch validation error - intronic variants

[Mighton, Chloe]

Hello, 

I tried running a batch of variants through the Mutalyzer name checker, and many of them had a similar error message: "Intronic position given for a non-genomic reference sequence. Tip: make use of a genomic reference sequence." However, the suggested reference sequence for most was the same as the reference sequence that was submitted, or the suggested reference sequence was NM_*. 

Please let me know how to resolve this issue. I have attached the output from mutalyzer for your reference. 

Thank you very much!

All the best,

Chloe

Chloe Mighton, MSc

Research Coordinator & Genomic Analyst

Department of Pathology & Laboratory Medicine,

Mount Sinai Hospital, Sinai Health ​

T: 647 808 2134

---

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[J.F.J. Laros]

Dear Chloe,

Thank you for using Mutalyzer.

The easiest way of getting to a genomic reference sequence is to use the
chromosome as a reference. E.g., transcript NM_002001.3 resides on chromosome
NC_000001.10, so an intronic variant in this transcript may look as follows.

NC_000001.10(NM_002001.3):c.76+1del

You may find the Position Converter [1] convenient for finding the chromosome
on which a transcript resides.


With kind regards,
Jeroen.

References:
[1] https://mutalyzer.nl/position-converter?assembly_name_or_alias=GRCh37&description=NM_002001.3%3Ac.76%2B1del

On Wed, Dec 30, 2020 at 05:18:43PM +0000, Mighton, Chloe wrote:
> Hello,
>
>
> I tried running a batch of variants through the Mutalyzer name checker, and
> many of them had a similar error message: "Intronic position given for a
> non-genomic reference sequence. Tip: make use of a genomic reference
> sequence." However, the suggested reference sequence for most was the same as
> the reference sequence that was submitted, or the suggested reference
> sequence was NM_*.
>
>
> Please let me know how to resolve this issue. I have attached the output from
> mutalyzer for your reference.
>
>
> Thank you very much!
>
>
> All the best,
>
> Chloe
>
>
> Chloe Mighton, MSc
> Research Coordinator & Genomic Analyst
> Department of Pathology & Laboratory Medicine,

> Mount Sinai Hospital, Sinai Health ?

> T: 647 808 2134
>
> ________________________________
> This e-mail may contain confidential and/or privileged information for the sole use of the intended recipient. If you are not the intended recipient, you are strictly prohibited from reviewing, copying or disclosing this e-mail. If you have received this e-mail in error, please immediately notify the sender and delete all copies.
>

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--
Jeroen F.J. Laros - J.F.J...@lumc.nl

[Johan T den Dunnen]

Dear Chloe,

the main problem is that you can not use the format
NM_002001.3:c.76+1del to describe a variant. The reference sequence you
use (NM_002001.3) does not contain the variant nucleotide (c.76+1) so
can not be used as a reference. This offends a basic HGVS nomenclature rule.

Best regards,

Johan den Dunnen
HGVS/HVP/HUGO sequence variant description working group
http://www.HGVS.org/varnomen
facebook.com/HGVSmutnomen