Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000888040 | SCV001031646 | likely benign | not provided | 2018-05-08 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994146 | SCV004813162 | uncertain significance | not specified | 2024-02-20 | criteria provided, single submitter | clinical testing | Variant summary: DPYD c.2915A>G (p.Gln972Arg) results in a conservative amino acid change located in the 4Fe-4S ferredoxin-type, iron-sulphur binding domain (IPR017896) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 251324 control chromosomes, predominantly at a frequency of 0.002 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 (0.00014 vs 0.0025), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2915A>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. The following publication has been ascertained in the context of this evaluation (PMID: 24648345). ClinVar contains an entry for this variant (Variation ID: 715550). Based on the evidence outlined above, the variant was classified as uncertain significance. |