ClinVar Miner

Submissions for variant NM_006397.3(RNASEH2A):c.323G>A (p.Arg108Gln)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001058397 SCV001222963 uncertain significance Aicardi Goutieres syndrome 4 2019-12-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 108 of the RNASEH2A protein (p.Arg108Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant also falls at the last nucleotide of exon 3 of the RNASEH2A coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Aicardi Goutieres syndrome (PMID: 25604658). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. 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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