Submissions for variant NM_014797.3(ZBTB24):c.1492_1493del (p.Gln498fs)

dbSNP: rs1131691654

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493496	SCV000582570	pathogenic	not provided	2015-08-29	criteria provided, single submitter	clinical testing	The c.1492_1493delCA deletion in the ZBTB24 gene has not been reported previously as a pathogenic variant nor as a benign polymorphism, to our knowledge. The c.1492_1493delCA variant causes a frameshift starting with codon Glutamine 498, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Gln498ValfsX15. This deletion is predicted to cause loss of normal protein function through protein truncation. The c.1492_1493delCA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1492_1493delCA as a pathogenic variant.
Breakthrough Genomics, Breakthrough Genomics	RCV004596230	SCV005088795	pathogenic	Immunodeficiency-centromeric instability-facial anomalies syndrome 2	2019-10-17	criteria provided, single submitter	clinical testing	This variant predicted to cause a frameshift and consequent premature termination of the protein (p.Gln498ValfsTer15). The truncated protein is likely to lack the C2H2-type 8 domain of the protein; this will likely result in loss-of-function. Functional studies explained that the loss of functional Zbtb24 results in the early embryonic lethality suggesting the loss-of-function of the corresponding protein [PMID: 27466202, 30085123]. The variant was previously reported as in a female patient indicative of ICF-2 syndrome with the initial clinical features of hypogammaglobulinemia and also presented with CMV pneumonitis and persistent CMV viremia [PMID: 30809743].