ClinVar Miner

Submissions for variant NM_015474.4(SAMHD1):c.625G>A (p.Gly209Ser)

gnomAD frequency: 0.00001  dbSNP: rs121434516
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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 RCV000004281 SCV000956910 likely pathogenic Aicardi-Goutieres syndrome 5 2023-11-20 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 209 of the SAMHD1 protein (p.Gly209Ser). This variant also falls at the last nucleotide of exon 5, which is part of the consensus splice site for this exon. This variant is present in population databases (rs121434516, gnomAD 0.0009%). This missense change has been observed in individuals with Aicardi-Goutières syndrome (PMID: 19525956, 27943079). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4066). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on SAMHD1 function (PMID: 22461318, 24035396, 28229507). 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 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.
OMIM RCV000004281 SCV000024447 pathogenic Aicardi-Goutieres syndrome 5 2009-07-01 no assertion criteria provided literature only
GeneReviews RCV000004281 SCV000147936 not provided Aicardi-Goutieres syndrome 5 no assertion provided literature only

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