Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781325 | SCV000919272 | likely benign | not specified | 2018-10-08 | criteria provided, single submitter | clinical testing | Variant summary: DPYD c.451A>G (p.Asn151Asp) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0016 in 276210 control chromosomes, predominantly within the Latino subpopulation at a frequency of 0.012 in the gnomAD database, including 2 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 4.8-fold over the estimated maximal expected allele frequency for a pathogenic variant in DPYD causing Dihydropyrimidine Dehydrogenase Deficiency phenotype (0.0025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.451A>G has been reported in the literature, however these reports do not provide unequivocal conclusions about association of the variant with Dihydropyrimidine Dehydrogenase Deficiency. At least one publication reports experimental evidence evaluating an impact on protein function, but does not allow convincing conclusions about the variant effect. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign. |
| Labcorp Genetics |
RCV000971168 | SCV001118794 | benign | not provided | 2019-12-31 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics | RCV000971168 | SCV001143796 | likely benign | not provided | 2018-10-02 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001106101 | SCV001263135 | uncertain significance | Dihydropyrimidine dehydrogenase deficiency | 2017-08-30 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |