ClinVar Miner

Submissions for variant NM_015474.4(SAMHD1):c.1411-2A>G

gnomAD frequency: 0.00001  dbSNP: rs515726141
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000114348 SCV001218442 pathogenic Aicardi-Goutieres syndrome 5 2023-09-21 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 12 of the SAMHD1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs515726141, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with cerebral vasculopathy and early onset of stroke (PMID: 21402907). ClinVar contains an entry for this variant (Variation ID: 126407). Studies have shown that disruption of this splice site results in skipping of exon 13, but is expected to preserve the integrity of the reading-frame (PMID: 21402907). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV003137627 SCV003827360 pathogenic not provided 2022-05-16 criteria provided, single submitter clinical testing
GeneDx RCV003137627 SCV005201557 pathogenic not provided 2023-11-27 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate skipping of exon 13 and degradation of the SAMHD1 protein in cell lysates from an affected individual (PMID: 21402907); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21633013, 31028937, 19525956, 28289923, 22461318, 34852373, 20301648, 21402907, 27943079)
GeneReviews RCV000114348 SCV000147924 not provided Aicardi-Goutieres syndrome 5 no assertion provided literature only

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