ClinVar Miner

Submissions for variant NM_000110.4(DPYD):c.2983G>T (p.Val995Phe)

dbSNP: rs1801268
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PharmGKB RCV000786704 SCV000925526 drug response fluorouracil response - Other 2021-03-24 reviewed by expert panel curation PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479218 SCV004223006 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2023-11-21 criteria provided, single submitter clinical testing Variant summary: DPYD c.2983G>T (p.Val995Phe) results in a non-conservative amino acid change located in the 4Fe-4S ferredoxin-type, iron-sulphur binding domain (IPR017896) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251376 control chromosomes (gnomAD). c.2983G>T has been reported in the literature in the homozygous state in an individual affected with Dihydropyrimidine Dehydrogenase Deficiency (Vreken_1998). At least two publications report experimental evidence evaluating an impact on protein function and found that the variant results in <12.5% enzymatic activity compared to the WT protein (e.g. Vreken_1998, Offer_2014). The following publications have been ascertained in the context of this evaluation (PMID: 24648345, 9686374). Based on the evidence outlined above, the variant was classified as likely pathogenic.

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