Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV002471653 | SCV002769091 | uncertain significance | Dihydropyrimidine dehydrogenase deficiency | 2020-06-11 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3A-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. However, heterozygous carriers of some variants may also show a reduction in dihydropyrimidine dehydrogenase activity and can be affected by 5-fluorouracil toxicity (PMID: 29152729, 26265346). (N) 0200 - Variant is predicted to result in a missense amino acid change from valine to alanine (exon 14). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (6 heterozygotes, 0 homozygotes). (P) 0501 - Missense variant consistently predicted to be damaging by multiple in-silico tools or highly conserved with a major amino acid change. (P) 0600 - Variant is located in an annotated domain or motif (Dihydropyrimidine dehydrogenase FMN-binding domain; NCBI). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0807 - Variant has not previously been reported in a clinical context. (N) 0905 - No segregation evidence has been identified for this variant. (N) 1002 - Moderate functional evidence supporting abnormal protein function. Functional studies show that this variant reduces enzyme activity (PMID: 29327356). (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |