exomiser_variant_tsv_output_CLINVAR_PRIMARY_INTERPRETATION_column, frequency scores and disease associations

[reversetosanam]

CLINVAR_PRIMARY_INTERPRETATION_column in .tsv output file shows 'not provided' instead of 'criteria provided, conflicting classifications', even in .html file there is showing 'no assertion criteria provided', please help with that

[reversetosanam]

even in CLINVAR_STAR_RATING column, 0 star is given by exomiser to the variants that are having conflicting classifications but it is usually 1 on clinvar database.

[julesjacobsen]

Can you provide the actual cases, please? Also, what is the version of the Exomiser data you're viewing? ClinVar is updated weekly whereas Exomiser is updated twice a year, so there will inevitably be some differences.

[reversetosanam]

Kindly check these columns in attached excel sheet.

I am using Exomiser 14.0.0, the latest one.

[julesjacobsen]

Ah! Thank you. Yes I see now.

These rows:

CLINVAR_VARIATION_ID	CLINVAR_PRIMARY_INTERPRETATION	CLINVAR_STAR_RATING
361482	NOT_PROVIDED	0
179002	NOT_PROVIDED	0
795060	NOT_PROVIDED	0
372319	NOT_PROVIDED	0

Should be:

CLINVAR_VARIATION_ID	CLINVAR_PRIMARY_INTERPRETATION	CLINVAR_STAR_RATING
361482	CONFLICTING_PATHOGENICITY_INTERPRETATIONS	1
179002	CONFLICTING_PATHOGENICITY_INTERPRETATIONS	1
795060	CONFLICTING_PATHOGENICITY_INTERPRETATIONS	1
372319	CONFLICTING_PATHOGENICITY_INTERPRETATIONS	1

I've found the cause - for some reason ClinVar changed the CLNSIG value for these from CLNSIG=Conflicting_interpretations_of_pathogenicity to CLNSIG=Conflicting_classifications_of_pathogenicity in the VCF files used to produce the Exomiser ClinVar data. Instead of failing, this fell back to the default value of NOT_PROVIDED.

[reversetosanam]

Thank you for looking into it, i hope it'll get resolved soon?

One more thing that i noticed in exomiser 14.0.0 annotations is the frequency data, it is not giving frequency data for some variants but i get it using other annotation tools like annovar and on the official databases as well like gnomad.

[reversetosanam]

and is it possible to get all phenotype associated diseases as per the phenoscore, the information is available in .html file but in variants.tsv file, disease with highest phenoscore is mentioned. Is it possible to add a column that mentions all associated diseases.

[julesjacobsen]

Thank you for looking into it, i hope it'll get resolved soon?

One more thing that i noticed in exomiser 14.0.0 annotations is the frequency data, it is not giving frequency data for some variants but i get it using other annotation tools like annovar and on the official databases as well like gnomad.

Examples please...

[julesjacobsen]

and is it possible to get all phenotype associated diseases as per the phenoscore, the information is available in .html file but in variants.tsv file, disease with highest phenoscore is mentioned. Is it possible to add a column that mentions all associated diseases.

Have you checked in the genes.tsv output?

[julesjacobsen]

ClinVar issues are fixed in #562 data. If you still have other issues, please open a separate ticket.