ClinVar Miner

Submissions for variant NM_014797.3(ZBTB24):c.1369C>T (p.Arg457Ter)

gnomAD frequency: 0.00001  dbSNP: rs387907106
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV000024092 SCV001424514 likely pathogenic Immunodeficiency-centromeric instability-facial anomalies syndrome 2 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000024092 SCV003923066 pathogenic Immunodeficiency-centromeric instability-facial anomalies syndrome 2 2023-03-14 criteria provided, single submitter clinical testing Variant summary: ZBTB24 c.1369C>T (p.Arg457X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. At least one truncation downstream of this position (c.1492_1493delCA/p.Gln498Valfs*15) has been classified as pathogenic in ClinVar and is reported in association with Immunodeficiency, centromeric instability and facial anomalies syndrome 2 in HGMD. The variant allele was found at a frequency of 1.2e-05 in 251446 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1369C>T has been reported in the literature in individuals affected with ICF Syndrome, Type 2 (e.g., deGreef_2011, Kamae_2018, Velasco_2014). These data indicate that the variant is likely to be associated with disease. Several publications report experimental evidence evaluating an impact on protein function, finding that the variant leads to centromeric instability and reduced promoter methylation at some genes (e.g., Kamae_2018, Velasco_2014, Velasco_2018). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000024092 SCV000045383 pathogenic Immunodeficiency-centromeric instability-facial anomalies syndrome 2 2011-06-10 no assertion criteria provided literature only

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