ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.209+5G>A

gnomAD frequency: 0.00001  dbSNP: rs754208761
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000698561 SCV000827231 likely pathogenic Werner syndrome 2024-01-24 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the WRN gene. It does not directly change the encoded amino acid sequence of the WRN protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs754208761, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 576138). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 3 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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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