ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.3819+5G>C

gnomAD frequency: 0.00008  dbSNP: rs770289356
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000234079 SCV000285570 uncertain significance Werner syndrome 2022-11-02 criteria provided, single submitter clinical testing This sequence change falls in intron 32 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 likely results in a shortened protein product. This variant is present in population databases (rs770289356, gnomAD 0.01%). 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: 238163). 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 32, but is expected to preserve the integrity of the reading-frame (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV000234079 SCV000897449 uncertain significance Werner syndrome 2018-10-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003407771 SCV004114758 uncertain significance WRN-related condition 2022-12-12 criteria provided, single submitter clinical testing The WRN c.3819+5G>C variant is predicted to interfere with splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-31012276-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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