Collecting recently failed variants as a list. please add

[Peter-J-Freeman]

chr5:112839840_112839842delGGCinsTGA b38

[Peter-J-Freeman]

19-40397933-ATCT-A b38
11-118505219-TTC-T b38
'5-177248182-G-A b38
chr10:g.102360218C>G b38

All seem to be the same error

Traceback (most recent call last):
File "/local/miniconda3/envs/vvweb_v2/lib/python3.10/site-packages/VariantValidator/modules/vvMixinCore.py", line 739, in validate
toskip = self._get_transcript_info(my_variant)
File "/local/miniconda3/envs/vvweb_v2/lib/python3.10/site-packages/VariantValidator/modules/vvMixinCore.py", line 1611, in _get_transcript_info
variant.gene_symbol = entry['hgnc_symbol']

NOTE: These are now fixed

[leicray]

The attached text file contains a long list of variants that have triggered ERROR messages from the interactive validation tool since the start of September this year.

Some of these might now be handled correctly since the recent patches.

variants that trigger error messages.txt

GRCh37 variants fixed

[leicray]

It looks like a user is trying to validate NM_024496.4:c.369_374del which does validate correctly in the interactive tool.

However, the error message says:

Internal Server Error: /bed/

TypeError at /bed/
create_bed_file() missing 5 required positional arguments: 'chromosome', 'build', 'genomic', 'vcf', and 'version'

That looks like the vcf2hgvs tool is being used. However, that would require the user to place the variant in a text file and then upload that file to the vcf2hgvs tool. Possible, but unlikely.

[Peter-J-Freeman]

Variant: 1-156138613-C-T

Hello, I'm having a problem validating the synonymous variant in LMNA (ClinVar ID 14500) - NM_170707.4(LMNA):c.1824C>T p.(Gly608=). I tried different ways, including chr1(GRCh38):g.156138613C>T and 1-156138613-C-T. Message error: Unable to validate the submitted variant against the GRCh38 assembly Thank you in advance.

[Peter-J-Freeman]

It looks like a user is trying to validate NM_024496.4:c.369_374del which does validate correctly in the interactive tool.

However, the error message says:

Internal Server Error: /bed/

TypeError at /bed/
create_bed_file() missing 5 required positional arguments: 'chromosome', 'build', 'genomic', 'vcf', and 'version'

That looks like the vcf2hgvs tool is being used. However, that would require the user to place the variant in a text file and then upload that file to the vcf2hgvs tool. Possible, but unlikely.

This is the code trying to create a UCSC link I believe. Not VCF. Thanks for logging it

[leicray]

Here is another one that ought not to trip up the system: NM_000179.3:c.4083dup

It generates error messages from the interactive service and submission to the batch tools also fails. The reference sequence is the MANE Select transcript for the MSH6 gene.

The traceback message for failure to validate via the batch tool is:

Traceback (most recent call last):
File "/local/py3Repos/variantValidator/VariantValidator/modules/vvMixinCore.py", line 752, in validate
toskip = mappers.transcripts_to_gene(my_variant, self, select_transcripts_dict_plus_version)
File "/local/py3Repos/variantValidator/VariantValidator/modules/mappers.py", line 643, in transcripts_to_gene
protein_dict = validator.myc_to_p(hgvs_coding, variant.evm, re_to_p=False, hn=variant.hn)
File "/local/py3Repos/variantValidator/VariantValidator/modules/vvMixinInit.py", line 535, in myc_to_p
start_aa = utils.one_to_three(aa_seq[0])
IndexError: string index out of range

In addition, this triggers a further exception:

Traceback (most recent call last):
File "/local/miniconda3/envs/vvweb_v2/lib/python3.10/site-packages/celery/app/trace.py", line 412, in trace_task
R = retval = fun(*args, **kwargs)
File "/local/miniconda3/envs/vvweb_v2/lib/python3.10/site-packages/celery/app/trace.py", line 704, in protected_call
return self.run(*args, **kwargs)
File "/local/VVweb/web/tasks.py", line 60, in batch_validate
output = validator.validate(variant, genome, transcripts)
File "/local/py3Repos/variantValidator/VariantValidator/modules/vvMixinCore.py", line 1462, in validate
raise fn.VariantValidatorError('Validation error')
VariantValidator.modules.utils.VariantValidatorError: Validation error

[Peter-J-Freeman]

Thanks. I think we have an issue open for debugging. Can you please add it. I want to do come debugging in a couple of weeks to release a new builod From: leicray ***@***.***> Date: Tuesday, 31 October 2023 at 09:33 To: openvar/variantValidator ***@***.***> Cc: Peter Freeman ***@***.***>, Author ***@***.***> Subject: Re: [openvar/variantValidator] Collecting recently failed variants as a list. please add (Issue #545) Here is another one that ought not to trip up the system: NM_000179.3:c.4083dup It generates error messages from the interactive service and submission to the batch tools also fails. The reference sequence is the MANE Select transcript for the MSH6 gene. The traceback message for failure to validate via the batch tool is: Traceback (most recent call last): File "/local/py3Repos/variantValidator/VariantValidator/modules/vvMixinCore.py", line 752, in validate toskip = mappers.transcripts_to_gene(my_variant, self, select_transcripts_dict_plus_version) File "/local/py3Repos/variantValidator/VariantValidator/modules/mappers.py", line 643, in transcripts_to_gene protein_dict = validator.myc_to_p(hgvs_coding, variant.evm, re_to_p=False, hn=variant.hn) File "/local/py3Repos/variantValidator/VariantValidator/modules/vvMixinInit.py", line 535, in myc_to_p start_aa = utils.one_to_three(aa_seq[0]) IndexError: string index out of range In addition, this triggers a further exception: Traceback (most recent call last): File "/local/miniconda3/envs/vvweb_v2/lib/python3.10/site-packages/celery/app/trace.py", line 412, in trace_task R = retval = fun(*args, **kwargs) File "/local/miniconda3/envs/vvweb_v2/lib/python3.10/site-packages/celery/app/trace.py", line 704, in protected_call return self.run(*args, **kwargs) File "/local/VVweb/web/tasks.py", line 60, in batch_validate output = validator.validate(variant, genome, transcripts) File "/local/py3Repos/variantValidator/VariantValidator/modules/vvMixinCore.py", line 1462, in validate raise fn.VariantValidatorError('Validation error') VariantValidator.modules.utils.VariantValidatorError: Validation error — Reply to this email directly, view it on GitHub [github.com]<https://urldefense.com/v3/__https:/github.com/openvar/variantValidator/issues/545*issuecomment-1786840459__;Iw!!PDiH4ENfjr2_Jw!FHx9A_rx_a9tND79UlqIDMpebg4S8W7HJ37ylSaiTJM8UjpmuSOiCtgKa7BsESnfYX5GJ9HO5QF136PHQjSHPJrYr1r32yS14jjSzDz7$>, or unsubscribe [github.com]<https://urldefense.com/v3/__https:/github.com/notifications/unsubscribe-auth/AGKWROOALHIL3I72Y4AVW7LYCDAWDAVCNFSM6AAAAAA4V7I47CVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMYTOOBWHA2DANBVHE__;!!PDiH4ENfjr2_Jw!FHx9A_rx_a9tND79UlqIDMpebg4S8W7HJ37ylSaiTJM8UjpmuSOiCtgKa7BsESnfYX5GJ9HO5QF136PHQjSHPJrYr1r32yS14iAYSCqb$>. You are receiving this because you authored the thread.Message ID: ***@***.***>

[leicray]

What do you mean by "add it"? This is the report.

[Peter-J-Freeman]

Sorry, I meant to the open git issue. You already collated a few variants that fail processing I believe?? Grant coming well. Should be able on time. Dr Peter Freeman Lecturer in Healthcare sciences (Clinical bioinformatics, genomics) Division of Informatics, Imaging & Data Science Faculty of Biology, Medicine and Health | The University of Manchester G.725 | Stopford Building | Oxford Road | Manchester | M13 9PT Tel: +44(0) 161 275 5731 email: ***@***.******@***.***> web: Peter Freeman<https://www.research.manchester.ac.uk/portal/peter.j.freeman.html> [A close-up of a logo Description automatically generated] website: www.manchester.ac.uk<http://www.manchester.ac.uk/> Social media: Facebook<https://www.facebook.com/TheUniversityOfManchester> Twitter<https://twitter.com/OfficialUoM> LinkedIn<https://www.linkedin.com/school/university-of-manchester/> Instagram<https://www.instagram.com/officialuom/> YouTube<http://www.youtube.com/user/universitymanchester> [VariantValidator Logo] web: www.variantvalidator.org<http://www.variantvalidator.org/> Social media: Twitter<https://twitter.com/intent/follow?ref_src=twsrc%5Etfw%7Ctwcamp%5Ebuttonembed%7Ctwterm%5Efollow%7Ctwgr%5EVariantValidatr&screen_name=VariantValidatr> Facebook<https://www.facebook.com/VariantValidator> Buy-us-a-coffee, supporting SWAN UK<https://www.buymeacoffee.com/VariantValidatr> From: leicray ***@***.***> Date: Tuesday, 31 October 2023 at 09:44 To: openvar/variantValidator ***@***.***> Cc: Peter Freeman ***@***.***>, Author ***@***.***> Subject: Re: [openvar/variantValidator] Collecting recently failed variants as a list. please add (Issue #545) What do you mean by "add it"? This is the report. — Reply to this email directly, view it on GitHub [github.com]<https://urldefense.com/v3/__https:/github.com/openvar/variantValidator/issues/545*issuecomment-1786860236__;Iw!!PDiH4ENfjr2_Jw!A2DE_rJKOiwaoSi0oA5VBfh8Q8L0zmh10q13s0bUmWxk8Rz9uNUg2TU141M9V4B7xAV1GJ2mBz88dn7oWA8VB7KtHbqrwLi-uIZ3j73U$>, or unsubscribe [github.com]<https://urldefense.com/v3/__https:/github.com/notifications/unsubscribe-auth/AGKWROI7MOHUS252ZZQATUTYCDB7JAVCNFSM6AAAAAA4V7I47CVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMYTOOBWHA3DAMRTGY__;!!PDiH4ENfjr2_Jw!A2DE_rJKOiwaoSi0oA5VBfh8Q8L0zmh10q13s0bUmWxk8Rz9uNUg2TU141M9V4B7xAV1GJ2mBz88dn7oWA8VB7KtHbqrwLi-uI96yXnE$>. You are receiving this because you authored the thread.Message ID: ***@***.***>

[leicray]

Here is another one that trips up the interactive and batch validators:

11:2587692del (GRCh38)

[Peter-J-Freeman]

Thanks @leicray . Realised its a git email this time. I'm gonna do a little debugging now. Need time away from grant writing

[leicray]

And another one:

chr5:g.125887814C>T (GRCh37)

[Peter-J-Freeman]

Will come back to this one NG_059281.1:g.4962G>C (GRCh38). It's a database issue. Missing records

[Peter-J-Freeman]

This one too NG_061374.1:g.11229T>C (b38)

[Peter-J-Freeman]

So, the issue was that RefSeq are not maintaining RefSeqGene lookup tables. I added code to get the data from the API on fails. These variants are not fixed, but will not be fixed live until I do a new database build