ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.654+4C>T

gnomAD frequency: 0.00003  dbSNP: rs769275170
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000560828 SCV000629737 uncertain significance Werner syndrome 2024-05-30 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the WRN gene. It does not directly change the encoded amino acid sequence of the WRN protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs769275170, gnomAD 0.03%). 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: 458494). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
GeneDx RCV001755811 SCV001996333 uncertain significance not provided 2019-10-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
PreventionGenetics, part of Exact Sciences RCV003979952 SCV004786389 likely benign WRN-related disorder 2022-11-22 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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