ClinVar Miner

Submissions for variant NM_003227.4(TFR2):c.2014C>T (p.Gln672Ter)

gnomAD frequency: 0.00005  dbSNP: rs1051249273
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779521 SCV000916168 uncertain significance Hemochromatosis type 3 2018-10-15 criteria provided, single submitter clinical testing The TFR2 c.2014C>T (p.Gln672Ter) variant is a stop-gained variant, that has been reported in one study and is found in a compound heterozygous state with another stop-gained variant in a single individual with hereditary hemochromatosis (Joshi et al. 2015). The variant is also found in two unaffected family members in a heterozygous state. Control data are unavailable for the p.Gln672Ter variant and is reported at a frequency of 0.000293 in the Latino population of the Genome Aggregation Database. Based on the evidence and due to the potential impact of stop-gained variants, the p.Gln672Ter variant is classified as a variant of unknown significance but suspicious for pathogenicity for hereditary hemochromatosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000812711 SCV000953034 pathogenic Hereditary hemochromatosis 2024-01-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln672*) in the TFR2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TFR2 are known to be pathogenic (PMID: 23600741, 26029709). This variant is present in population databases (no rsID available, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with hereditary hemochromatosis (PMID: 26029709). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 632495). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000779521 SCV002018955 pathogenic Hemochromatosis type 3 2021-09-28 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003411720 SCV004106306 pathogenic TFR2-related condition 2023-04-27 criteria provided, single submitter clinical testing The TFR2 c.2014C>T variant is predicted to result in premature protein termination (p.Gln672*). This variant has previously been reported to be causative for hemochromatosis, type 3 (Joshi et al. 2015. PubMed ID: 26029709; Hernández et al. 2021. PubMed ID: 34946929). This variant is reported in 0.028% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-100224508-G-A). Nonsense variants in TFR2 are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics RCV000779521 SCV004203687 pathogenic Hemochromatosis type 3 2023-06-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV000779521 SCV002079929 pathogenic Hemochromatosis type 3 2021-02-05 no assertion criteria provided clinical testing

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