ClinVar Miner

Submissions for variant NM_000500.9(CYP21A2):c.1217G>A (p.Trp406Ter)

gnomAD frequency: 0.00001  dbSNP: rs151344503
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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 RCV001851812 SCV002227699 pathogenic not provided 2023-09-03 criteria provided, single submitter clinical testing This variant disrupts a region of the CYP21A2 protein in which other variant(s) (p.Gln482*) have been determined to be pathogenic (PMID: 24799024, 30048636; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 12171). This variant is also known as p.W405X. This premature translational stop signal has been observed in individuals with classic salt-wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency (PMID: 8518786, 20926536, 23359698). The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change creates a premature translational stop signal (p.Trp406*) in the CYP21A2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 90 amino acid(s) of the CYP21A2 protein. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012953 SCV000033197 pathogenic Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency 1993-05-01 no assertion criteria provided literature only

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