ClinVar Miner

Submissions for variant NM_000500.9(CYP21A2):c.1451G>C (p.Arg484Pro)

gnomAD frequency: 0.00039  dbSNP: rs200005406
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Endocrinology Laboratory, Christian Medical College RCV001667859 SCV001890903 likely pathogenic Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003238376 SCV002009126 pathogenic not provided 2021-11-03 criteria provided, single submitter clinical testing
3billion RCV001667859 SCV002521480 likely pathogenic Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.033%). However, frequency data for this variant in the general population cannot be distinguished from that of the CYP21P pseudogene, and are therefore uninformative in assessment of variant pathogenicity. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.66; 3Cnet: 0.29). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV001264335). A different missense change at the same codon (p.Arg484Gln, p.Arg484Trp) has been reported to be associated with CYP21A2 related disorder (ClinVar ID: VCV000585750 / PMID: 12915679, 14715874). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003238376 SCV004221767 pathogenic not provided 2015-08-25 criteria provided, single submitter clinical testing The CYP21A2 c.1451G>C (p.Arg484Pro) pathogenic variant (also known as R483P) has been described to cause markedly decreased CYP21A2 activity and stability, and identified in individuals with CAH, mainly of the salt-wasting phenotype (PMID: 9497336 (1998), 15994751 (2005), 20926536 (2011), and 23359698 (2013), 32616876 (2020)). Based on the available information, this variant is classified as pathogenic.
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital RCV001667859 SCV002496415 uncertain significance Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency 2021-03-10 flagged submission clinical testing

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