ClinVar Miner

Submissions for variant NM_000320.3(QDPR):c.436+2552A>G

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005200443 SCV005834678 pathogenic Dihydropteridine reductase deficiency 2024-02-11 criteria provided, single submitter clinical testing This sequence change falls in intron 4 of the QDPR gene. It does not directly change the encoded amino acid sequence of the QDPR protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (PMID: 9341885). It has also been observed to segregate with disease in related individuals. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005200443 SCV005888034 pathogenic Dihydropteridine reductase deficiency 2025-01-07 criteria provided, single submitter clinical testing Variant summary: QDPR c.436+2552A>G is located at a position not widely known to affect splicing. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a 5' cryptic donor site. One predict the variant strengthens a 3' cryptic acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing by introducing a 152 bp pseudoexon containing an early stop codon (Ikeda_1997). The variant was absent in 31400 control chromosomes. c.436+2552A>G has been reported in the literature in two siblings affected with Dihydropteridine Reductase Deficiency (Ikeda_1997). These data indicate that the variant may be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 9341885). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic.

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