ClinVar Miner

Submissions for variant NM_000110.4(DPYD):c.1863G>A (p.Trp621Ter)

gnomAD frequency: 0.00001  dbSNP: rs1057516388
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409426 SCV000485577 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2016-01-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000409426 SCV001467803 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2020-12-02 criteria provided, single submitter clinical testing Variant summary: DPYD c.1863G>A (p.Trp621X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 1.2e-05 in 251336 control chromosomes. c.1863G>A has been reported in the literature as a de-novo mutation in an individual affected with schizophrenia (e.g. Xu_2012). The variant was also found in a cancer patient who experienced toxicity following treatment with fluoropyrimidine (e.g. Yokoi_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneDx RCV003236797 SCV003935607 likely pathogenic not provided 2023-06-21 criteria provided, single submitter clinical testing De novo variant in a patient with schizoaffective disorder, however, it is unclear if this patient had variants identified in other genes, and additional research is needed to explore this possible association (Xu et al., 2011); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23042115, 31589614, 25420024)
Genome-Nilou Lab RCV000409426 SCV004049536 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2023-04-11 criteria provided, single submitter clinical testing

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