ClinVar Miner

Submissions for variant NM_005585.5(SMAD6):c.817+4A>G

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003318981 SCV004022909 uncertain significance not provided 2023-07-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge; De novo variant with confirmed parentage in a proband referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene
Labcorp Genetics (formerly Invitae), Labcorp RCV003647977 SCV004449521 uncertain significance Aortic valve disease 2 2024-01-15 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the SMAD6 gene. It does not directly change the encoded amino acid sequence of the SMAD6 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. ClinVar contains an entry for this variant (Variation ID: 2574399). 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 may disrupt the consensus splice site. 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.

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