Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779011 | SCV000915452 | uncertain significance | Dihydropyrimidine dehydrogenase deficiency | 2017-12-18 | criteria provided, single submitter | clinical testing | The DPYD c.1764delC (p.Arg589GlufsTer20) variant results in a frameshift, and is predicted to result in premature termination of the protein. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. The variant is reported at a frequency of 0.000058 in the East Asian population from the Genome Aggregation Database but this is based on one allele so the variant is presumed to be rare. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for dihydropyrimidine dehydrogenase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000779011 | SCV002598548 | likely pathogenic | Dihydropyrimidine dehydrogenase deficiency | 2022-09-27 | criteria provided, single submitter | clinical testing | Variant summary: DPYD c.1764delC (p.Arg589GlufsX20) 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 associated with Dihydropyrimidine dehydrogenase deficiency in HGMD. The variant allele was found at a frequency of 4e-06 in 251048 control chromosomes. To our knowledge, no occurrence of c.1764delC in individuals affected with Dihydropyrimidine Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000779011 | SCV004194118 | likely pathogenic | Dihydropyrimidine dehydrogenase deficiency | 2023-04-25 | criteria provided, single submitter | clinical testing |