DPYD phenotype assigment

[ursikajanzic]

Hi, I have a question regarding the DPYD phenotype assignment in PharmCATv3.2.0.

For the following diplotype [c.85T>C (*9A) + c.496A>G] / [c.85T>C (*9A) + c.496A>G]

PharmCAT reports Indeterminate phenotype,

(this is a copy from .tsv file): DPYD [c.85T>C (*9A) + c.496A>G]/[c.85T>C (*9A) + c.496A>G] Indeterminate [c.85T>C (*9A) + c.496A>G] Unassigned function[c.85T>C (*9A) + c.496A>G] Unassigned function no 4 no c.85T>C (*9A)/c.85T>C (*9A) Normal Metabolizer 2.0

similar is for another sample: DPYD Reference/[c.85T>C (*9A) + c.496A>G] Indeterminate Reference Normal function 1.0 [c.85T>C (*9A) + c.496A>G] Unassigned function no 85 no Reference/c.85T>C (*9A) Normal Metabolizer 2.0

When considering the individual variants, they appear to be classified as normal/non-actionable in ClinPGx/CPIC resourcesand are reported as normal metabolizer

Could you clarify why the presence of c.496A>G causes PharmCAT to assign an Indeterminate phenotype instead of a normal metabolizer phenotype?

Thank you

[whaleyr]

I'm having a problem reproducing your issue.

If I create a synthetic VCF with just the two positions for c.85 and c.496 hom alt then I get Normal Metabolizer as the assigned phenotype. If I set the rest of the positions in DPYD to hom ref then I get the same result.

Can you send along an anonymized/synthetic example of the report or the VCF file that demonstrates the issue?