ClinVar Miner

Submissions for variant NM_000110.4(DPYD):c.1358C>G (p.Pro453Arg)

gnomAD frequency: 0.00031  dbSNP: rs144395748
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000086481 SCV001826382 uncertain significance not provided 2024-10-15 criteria provided, single submitter clinical testing Reported previously as heterozygous in one healthy individual of African American Ancestry; this individual's enzyme activity was not significantly different from that of a non-carrier (PMID: 23588312); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32707991, 23588312, 39032822)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222385 SCV002500594 uncertain significance not specified 2022-03-23 criteria provided, single submitter clinical testing Variant summary: DPYD c.1358C>G (p.Pro453Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.8e-05 in 250586 control chromosomes, predominantly at a frequency of 0.0014 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in DPYD causing Dihydropyrimidine Dehydrogenase Deficiency (8.8e-05 vs 0.0025), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1358C>G in individuals affected with Dihydropyrimidine Dehydrogenase Deficiency has been reported. At least one publication reports experimental evidence evaluating an impact on protein function (Offer_2014) These results showed no damaging effect of this variant. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV003343636 SCV004049548 uncertain significance Dihydropyrimidine dehydrogenase deficiency 2023-04-11 criteria provided, single submitter clinical testing
Diasio Lab, Mayo Clinic RCV000086481 SCV000118647 not provided not provided no assertion provided not provided

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