Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230873 | SCV003928788 | likely pathogenic | Dihydropyrimidine dehydrogenase deficiency | 2023-04-11 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exon 19 in the DPYD gene. A presumed nomenclature of c.(2299+1_2300-1)_(2442+1_2443-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a frameshift in the DPYD gene, a known mechanism of disease. The variant was absent in 21694 control chromosomes (gnomAD, Structural Variants dataset). To our knowledge, no occurrence of c.(2299+1_2300-1)_(2442+1_2443-1)del in individuals affected with Dihydropyrimidine Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. However, a splice variant at the donor splicing site of exon 19 (c.2242+1G>T) was demonstrated to result in exon 19 skipping at the RNA level, and was reported in an individual who experienced 5-fluoropyrimidine toxicity (PMID 30349384). No submitters have provided clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |