ClinVar Miner

Submissions for variant NM_000320.3(QDPR):c.68G>A (p.Gly23Asp)

gnomAD frequency: 0.00001  dbSNP: rs104893863
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pediatrics, Sichuan Provincial Hospital For Women And Children RCV003153240 SCV003840211 likely pathogenic Hyperphenylalaninemia due to tetrahydrobiopterin deficiency criteria provided, single submitter research proband，female, 1 month old, preliminary screening 358umol/L, erythrocytic dihydroteredine reductase determination 0.84nmol/ (min.5mmdisc) decreased, 40 days confirmed DHPRD
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000000519 SCV004020556 pathogenic Dihydropteridine reductase deficiency 2023-06-21 criteria provided, single submitter clinical testing Variant summary: QDPR c.68G>A (p.Gly23Asp) results in a non-conservative amino acid change to a highly conserved residue (HGMD) in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 236940 control chromosomes (gnomAD). c.68G>A has been reported in the literature in multiple homozygous individuals affected with Dihydropteridine Reductase Deficiency (Dianzani_1998, Farrigua_2007), and at least one compound heterozygous individual with another pathogenic variant. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding a severe reduction in enzymatic activity in vitro (Zhang_1996). The following publications have been ascertained in the context of this evaluation (PMID: 9744478, 17188538). One submitter has cited a clinical-significance assessment for this variant to ClinVar after 2014 and classified it as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000000519 SCV004293175 pathogenic Dihydropteridine reductase deficiency 2024-09-06 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 23 of the QDPR protein (p.Gly23Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biopterin-deficient hyperphenylalaninemia (PMID: 8326489, 8518287, 27246466). ClinVar contains an entry for this variant (Variation ID: 490). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects QDPR function (PMID: 8518287). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000000519 SCV005662075 pathogenic Dihydropteridine reductase deficiency 2024-05-24 criteria provided, single submitter clinical testing
OMIM RCV000000519 SCV000020668 pathogenic Dihydropteridine reductase deficiency 1993-06-01 no assertion criteria provided literature only

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