ClinVar Miner

Submissions for variant NM_005859.5(PURA):c.703del (p.Val235fs)

dbSNP: rs1763053563
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Genomics Program, Stanford Medicine RCV001253768 SCV001427064 pathogenic PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome 2019-07-10 no assertion criteria provided clinical testing The p.Val235Trpfs*12 variant in the PURA gene was identified de novo in this individual, but has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The p.Val235Trpfs*12 variant results in a 1bp deletion, which causes a shift in the protein reading frame, leading to a premature termination codon 12 amino acids downstream. There is only one coding exon in the PURA gene, therefore premature termination at this location is not predicted to result in nonsense-mediated decay. However, other truncating variants have been reported as disease-causing, including variants that truncate the protein downstream of this variant, suggesting that this variant disrupts gene function. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Val235Trpfs*12 variant as pathogenic for autosomal dominant PURA-related neurodevelopmental disorder based on the information above. [ACMG evidence codes used: PVS1_Strong; PS2; PM2]

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