Help with error codes

[Matteson, Jamie@CDPH]

Hello!

 

I was wondering if you could assist me in resolving a few errors/warnings.

 

For the following variants, I am getting, “(variantchecker): Intronic position given for a non-genomic reference sequence. Tip: make use of a genomic reference sequence, e.g., NC_000023.11(NM_000033.3), NC_000023.10(NM_000033.3).”

 

NM_000033.3:c.[1394-1G>C;289C>T]

NM_000033.3:c.1225-1G>A

NM_000033.3:c.1866-10G>A

NM_000033.3:c.1489-6delC

NM_000033.3:c.901-1G>A

NM_000033.3:c.1082-4G>A

NM_000033.3:c.1393+1G>T

NM_000033.3:c.1635-6C>T

NM_000033.3:c.1991_1991+13delGGTAGGTGCCCTGT

NM_000033.3:c.1992-2A>G

 

I am also getting, “(GenRecord): Mutation in start codon of gene ABCD1 transcript 001.” for NM_000033.3:c.3G>T

 

And, “(grammar): Expected "]" (at char 21), (line:1, col:22)” for NM_000033.3:c.[139C>T;c.148G>C]

 

And, “(grammar): Expected "IVS" (at char 12), (line:1, col:13)” for NM_000033.3:C.1771C>T

 

And, “(variantchecker): Position c.*16047 (g.18684) is outside of the sequence range [1, 3697]. Tip: make use of a genomic reference sequence, e.g., NC_000023.11(NM_000033.3), NC_000023.10(NM_000033.3).” for NM_000033.3:c.18285A>G

 

Thank you in advance,

 

Jamie Matteson, MPH

Genetic Disease Screening Program

California Department of Public Health

850 Marina Bay Parkway, F-175, MS-8200

Richmond, CA 94804

Phone: 707.287.2284

Fax: 510.412.1560

jamie.m...@cdph.ca.gov

 

 

[J.F.J. Laros]

Dear Jamie,

Thank you for using Mutalyzer.

For your first question, please see this [1] discussion.

The mutation is the start codon is only a warning for the user to indicate that
the protein is likely to be absent.

NM_000033.3:c.[139C>T;c.148G>C] should be written as NM_000033.3:c.[139C>T;148G>C]

In your last example, Mutalyzer is asked to do something with a position that
is larger than the reference sequence. It can therefore do nothing sensible.

I hope this helps.


With kind regards,
Jeroen.

References:
[1] https://groups.google.com/g/mutalyzer/c/g4wB4grBkgk

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

[Matteson, Jamie@CDPH]

Hi Jeroen,

Thank you so much for your help. The Mutalyzer and your consultation are such amazing resources to have.

Forgive me for my lack of understanding, but for the last example, is it likely that our laboratory provided us with a typo on the variant, since it is so much larger than the sequence range? For example, maybe it should be c.1828A>G instead of c.18285A>G?

Also, for NM_000033.3:C.1771C>T, should it be written NM_000033.3:IVSc.1771C>T? Do you happen to have a reference for why that is?

Thank you again for your time,

-Jamie

-----Original Message-----
From: J.F.J. Laros <J.F.J...@lumc.nl>
Sent: Friday, January 22, 2021 12:29 AM
To: Matteson, Jamie@CDPH <Jamie.M...@cdph.ca.gov>
Cc: muta...@googlegroups.com
Subject: Re: [mutalyzer] Help with error codes

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Dear Jamie,

Thank you for using Mutalyzer.

For your first question, please see this [1] discussion.

The mutation is the start codon is only a warning for the user to indicate that the protein is likely to be absent.

NM_000033.3:c.[139C>T;c.148G>C] should be written as NM_000033.3:c.[139C>T;148G>C]

In your last example, Mutalyzer is asked to do something with a position that is larger than the reference sequence. It can therefore do nothing sensible.

I hope this helps.


With kind regards,
Jeroen.

References:

[1] https://urldefense.proofpoint.com/v2/url?u=https-3A__groups.google.com_g_mutalyzer_c_g4wB4grBkgk&d=DwIBAg&c=Lr0a7ed3egkbwePCNW4ROg&r=GW9Ux6pOBa1Vx1pVJmot4fkyk0gNYv34jTAY2JGuvsw&m=ClrPvHswJvkH0ksKkcAwVuAXJH_Jobb7_lbRUN5J6JI&s=aeN4j2rEwKne30HpDJkF-xSgyZ5yzP4DXCTTcBhVGzY&e=

> To view this discussion on the web visit https://urldefense.proofpoint.com/v2/url?u=https-3A__groups.google.com_d_msgid_mutalyzer_BY5PR09MB59541E516C14F29C1C6CEDD3C6A19-2540BY5PR09MB5954.namprd09.prod.outlook.com&d=DwIBAg&c=Lr0a7ed3egkbwePCNW4ROg&r=GW9Ux6pOBa1Vx1pVJmot4fkyk0gNYv34jTAY2JGuvsw&m=ClrPvHswJvkH0ksKkcAwVuAXJH_Jobb7_lbRUN5J6JI&s=PYPTvkUR-aZFIWLyhAojm2a9Hny3VhA0JFx3fTEQVwY&e= .

[J.F.J. Laros]

Dear Jamie,

My guess is that the variant has been called on a genomic reference and has
been converted (incorrectly) to a description on a transcript. It is probably
better to submit the original chromosomal variant description here.

As for your second question, "C." should be written as "c." to correct the
description.


With kind regards,
Jeroen.

> To view this discussion on the web visit https://groups.google.com/d/msgid/mutalyzer/BY5PR09MB59542E0599A83A3C869A5588C6A09%40BY5PR09MB5954.namprd09.prod.outlook.com.

[Matteson, Jamie@CDPH]

Thank you! That resolved the existing error codes. One more came up that I'm not sure what to do with, though:

NC_000023.10(NM_000033.3):c.1991_1991+13delGGTAGGTGCCCTGT

(variantchecker): Variant hits one or more splice sites in selected transcript.

Your advice is greatly appreciated.

> To view this discussion on the web visit https://urldefense.proofpoint.com/v2/url?u=https-3A__groups.google.com_d_msgid_mutalyzer_BY5PR09MB59542E0599A83A3C869A5588C6A09-2540BY5PR09MB5954.namprd09.prod.outlook.com&d=DwIDaQ&c=Lr0a7ed3egkbwePCNW4ROg&r=GW9Ux6pOBa1Vx1pVJmot4fkyk0gNYv34jTAY2JGuvsw&m=HjDotkWoYWrzHY2cchgss9ID-HSRbdtAoqnnEoV8XMA&s=EDH2YSs-yBYAlNfLFWTixxuHSq0s4OidMYymXTP9IsY&e= .

[J.F.J. Laros]

Dear Jamie,

All messages marked in yellow are warnings. These are usually given to inform
users that care needs to be taken when interpreting the effect of a variant.
The description itself is correct.


With kind regards,
Jeroen.

> To view this discussion on the web visit https://groups.google.com/d/msgid/mutalyzer/BY5PR09MB595461FC38B50FF3901D707CC6A09%40BY5PR09MB5954.namprd09.prod.outlook.com.

[Matteson, Jamie@CDPH]

I see. Thanks very much for all of your help.

> To view this discussion on the web visit https://urldefense.proofpoint.com/v2/url?u=https-3A__groups.google.com_d_msgid_mutalyzer_BY5PR09MB595461FC38B50FF3901D707CC6A09-2540BY5PR09MB5954.namprd09.prod.outlook.com&d=DwIDaQ&c=Lr0a7ed3egkbwePCNW4ROg&r=GW9Ux6pOBa1Vx1pVJmot4fkyk0gNYv34jTAY2JGuvsw&m=U2nSzr97P1kWJQ13j7U3lQb9XIrqdVpy60LhViz_S8Y&s=BcxJNKIzG6ST-RKxrTnnjwyIJPfi_M0aBWzywVsHWis&e= .