ClinVar Miner

Submissions for variant NM_002163.4(IRF8):c.433G>A (p.Glu145Lys)

gnomAD frequency: 0.00001  dbSNP: rs755978434
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001221642 SCV001393701 uncertain significance Immunodeficiency 32B; Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency 2022-05-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 145 of the IRF8 protein (p.Glu145Lys). This variant is present in population databases (rs755978434, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with IRF8-related conditions. ClinVar contains an entry for this variant (Variation ID: 950027). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV004629493 SCV005124404 uncertain significance Inborn genetic diseases 2024-05-24 criteria provided, single submitter clinical testing The c.433G>A (p.E145K) alteration is located in exon 4 (coding exon 3) of the IRF8 gene. This alteration results from a G to A substitution at nucleotide position 433, causing the glutamic acid (E) at amino acid position 145 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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