ClinVar Miner

Submissions for variant NM_000486.5(AQP2):c.763C>T (p.Gln255Ter) (rs370879515)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000384617 SCV000338801 pathogenic not provided 2016-01-21 criteria provided, single submitter clinical testing
Invitae RCV000384617 SCV001210069 likely pathogenic not provided 2020-06-29 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the AQP2 gene (p.Gln255*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acids of the AQP2 protein. This variant is present in population databases (rs370879515, ExAC 0.003%). This variant has not been reported in the literature in individuals with AQP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 285666). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Pro262 amino acid residue in AQP2. Other variant(s) that disrupt this residue have been observed in individuals with AQP2-related conditions (PMID: 9550615, 15509592), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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