ClinGen Allele Registry API seems to have problems retrieving data

[clinicalngs]

Describe the bug
ClinGen Allele Registry API returns errors about retrieving data from ClinGen database

To Reproduce
Annotate a vcf (HG38) with ClinGen Allele Registry Module (version Posted on: 2/18/2025)
Look at error file generated by OpenCravat to see the list of errors.

Expected behavior
For each variant there should be some info about the variant retrieved from the ClinGen website it that variant exists in the database, or no info if the variant is absent.

Screenshots
Here is a piece of the errors:

SOURCE:error.clingen_allele_registry
[2068]2069 chr1 1385553 G A CCNL2 ENST00000400809.8 2KD c.*1678C>T {"CCNL2": [["Q96S94", "", "2KD", "ENST00000400809.8", "c.*1678C>T"], ["", "", "2KD", "ENST00000408952.8", "c.*1678C>T"], ["Q96S94", "", "2KD,NMD", "ENST00000481223.6", "c.*3254C>T"], ["Q96S94", "", "2KD,NMD", "ENST00000488340.5", "c.*2571C>T"], ["", "", "2KD,PTR", "ENST00000505849.5", ""]]} 1385553
(500 Server Error: InternalServerError for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000400809.8:c.*1678C%3ET)

SOURCE:error.clingen_allele_registry
[2083]2084 chr1 1427995 A G TMEM88B ENST00000378821.3 2KD c.*208A>G {"TMEM88B": [["A6NKF7", "", "2KD", "ENST00000378821.3", "c.*208A>G"]]} 1427995
(500 Server Error: InternalServerError for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000378821.3:c.*208A%3EG)

SOURCE:error.clingen_allele_registry
[2084]2085 chr1 1428031 - G TMEM88B ENST00000378821.3 2KD c.*247dup {"TMEM88B": [["A6NKF7", "", "2KD", "ENST00000378821.3", "c.*247dup"]]} 1428031
(500 Server Error: InternalServerError for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000378821.3:c.*247dup)

SOURCE:error.clingen_allele_registry
[2085]2086 chr1 1428121 - AGGGGAGGGCAGGGGAAGAGAGGGGCGGGGAGGGGAGGGGAAGAGAGGGT TMEM88B ENST00000378821.3 2KD c.*342_*343insCAGGGGAAGAGAGGGGCGGGGAGGGGAGGGGAAGAGAGGGTAGGGGAGGG {"TMEM88B": [["A6NKF7", "", "2KD", "ENST00000378821.3", "c.*342_*343insCAGGGGAAGAGAGGGGCGGGGAGGGGAGGGGAAGAGAGGGTAGGGGAGGG"]]} 1428170
(500 Server Error: InternalServerError for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000378821.3:c.*342_*343insCAGGGGAAGAGAGGGGCGGGGAGGGGAGGGGAAGAGAGGGTAGGGGAGGG)

SOURCE:error.clingen_allele_registry
[2086]2087 chr1 1429954 A G LINC01770 ENST00000417917.1 LNC {"LINC01770": [["", "", "2KD,LNC", "ENST00000417917.1", ""], ["", "", "2KD,LNC", "ENST00000430109.1", ""], ["", "", "2KD,LNC", "ENST00000434150.1", ""], ["", "", "2KD,LNC", "ENST00000454562.1", ""]]} 1429954
(400 Client Error: BadRequest for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000417917.1:None)

SOURCE:error.clingen_allele_registry
[2087]2088 chr1 1433219 A C LINC01770 ENST00000417917.1 LNC {"LINC01770": [["", "", "INT,LNC", "ENST00000417917.1", ""], ["", "", "INT,LNC", "ENST00000430109.1", ""], ["", "", "2KU,LNC", "ENST00000434150.1", ""], ["", "", "INT,LNC", "ENST00000454562.1", ""]]} 1433219
(400 Client Error: BadRequest for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000417917.1:None)

SOURCE:error.clingen_allele_registry
[2088]2089 chr1 1433267 A T LINC01770 ENST00000417917.1 LNC {"LINC01770": [["", "", "INT,LNC", "ENST00000417917.1", ""], ["", "", "INT,LNC", "ENST00000430109.1", ""], ["", "", "2KU,LNC", "ENST00000434150.1", ""], ["", "", "INT,LNC", "ENST00000454562.1", ""]]} 1433267
(400 Client Error: BadRequest for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000417917.1:None)

SOURCE:error.clingen_allele_registry
[2090]2091 chr1 1442856 - ATAAACCAAGTCAATTTTCTATAGTGACGGTG VWA1 ENST00000476993.2 UT3 3 c.*3121_*3152dup {"VWA1": [["Q6PCB0", "", "UT3", "ENST00000476993.2", "c.*3121_*3152dup"]]} 1442887
(500 Server Error: InternalServerError for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000476993.2:c.*3121_*3152dup)

SOURCE:error.clingen_allele_registry
[2091]2092 chr1 1443133 T C VWA1 ENST00000476993.2 2KD c.*3346T>C {"VWA1": [["Q6PCB0", "", "2KD", "ENST00000476993.2", "c.*3346T>C"]]} 1443133
(500 Server Error: InternalServerError for url: https://reg.clinicalgenome.org/allele?hgvs=ENST00000476993.2:c.*3346T%3EC)

Desktop (please complete the following information):

• Win10 updated
• Chrome latest
• OpenCravat 2.11.1 (w. updated ClinGen Gene and Allele Registry modules)

Additional context
Not sure who is in charge of ClinGen modules.
But their website works, as I tested some error-generating variants according to web instructions (e.g. for variant [chr1 1443133 T C ] from gene VWA1 - the last in the example above), and the variants are found.

[skanderson]

Thank you for the report. These errors seem to an oddity in transcription mapping on our end, but I'm not sure the root cause quite yet. We are looking into it.