ClinVar Miner

Submissions for variant NM_003227.4(TFR2):c.2374G>A (p.Gly792Arg)

gnomAD frequency: 0.00006  dbSNP: rs80338891
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494525 SCV000583030 likely pathogenic not provided 2018-03-20 criteria provided, single submitter clinical testing The G792R variant in the TFR2 gene has been reported previously in the homozygous and compound heterozygous state in individuals affected with hemochromatosis (Joshi et al., 2015; Lee et al., 2006). The G792R variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G792R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Glycine are tolerated across species. Cellular protein localization studies using immunofluorescence demonstrate that the G792R variant impairs the plasma membrane localization of TFR2 (Joshi et al., 2015). The G792R variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Labcorp Genetics (formerly Invitae), Labcorp RCV001219293 SCV001391226 likely pathogenic Hereditary hemochromatosis 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 792 of the TFR2 protein (p.Gly792Arg). This variant is present in population databases (rs80338891, gnomAD 0.01%). This missense change has been observed in individuals with hereditary hemochromatosis in a family and has also been observed in several affected individuals (PMID: 16424658, 26029709). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 21374). 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. 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.
Fulgent Genetics, Fulgent Genetics RCV000020547 SCV002777257 likely pathogenic Hemochromatosis type 3 2024-03-28 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000020547 SCV003811542 likely pathogenic Hemochromatosis type 3 2022-04-29 criteria provided, single submitter clinical testing
Baylor Genetics RCV000020547 SCV004203667 likely pathogenic Hemochromatosis type 3 2024-03-25 criteria provided, single submitter clinical testing
GeneReviews RCV000020547 SCV000041014 not provided Hemochromatosis type 3 no assertion provided literature only
Natera, Inc. RCV000020547 SCV002079915 likely pathogenic Hemochromatosis type 3 2020-07-20 no assertion criteria provided clinical testing

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