ClinVar Miner

Submissions for variant NM_001572.5(IRF7):c.766G>T (p.Gly256Cys)

dbSNP: rs369330126
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000695228 SCV000823714 uncertain significance Immunodeficiency 39 2018-05-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 269 of the IRF7 protein (p.Gly269Cys). The glycine residue is weakly conserved and there is a large physicochemical difference between glycine and cysteine. This variant also falls at the last nucleotide of exon 5 of the IRF7 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 not been reported in the literature in individuals with IRF7-related disease. 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: "Deleterious"; PolyPhen-2: "Probably 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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