ClinVar Miner

Submissions for variant NM_000110.4(DPYD):c.2275C>T (p.Arg759Ter)

gnomAD frequency: 0.00004  dbSNP: rs759372918
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409049 SCV000486155 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2016-04-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000409049 SCV000894211 pathogenic Dihydropyrimidine dehydrogenase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000409049 SCV001362329 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2023-03-21 criteria provided, single submitter clinical testing Variant summary: DPYD c.2275C>T (p.Arg759X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 2.8e-05 in 250742 control chromosomes. c.2275C>T has been reported in the literature, however with limited phenotypic information (e.g. Hesse_2018). This report does not provide unequivocal conclusions about association of the variant with Dihydropyrimidine Dehydrogenase Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Genetic Services Laboratory, University of Chicago RCV001821134 SCV002064498 likely pathogenic not provided 2017-10-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000409049 SCV004049526 likely pathogenic Dihydropyrimidine dehydrogenase deficiency 2023-04-11 criteria provided, single submitter clinical testing
GeneDx RCV001821134 SCV004167919 likely pathogenic not provided 2023-10-22 criteria provided, single submitter clinical testing Reported in a patient with a suspected epilepsy syndrome (Hesse et al., 2018); 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; This variant is associated with the following publications: (PMID: 25087612, 29778030)
Baylor Genetics RCV000409049 SCV004194117 pathogenic Dihydropyrimidine dehydrogenase deficiency 2023-05-05 criteria provided, single submitter clinical testing

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