Submissions for variant NM_001367624.2(ZNF469):c.7294C>T (p.Gln2432Ter)

gnomAD frequency: 0.00001  dbSNP: rs1906450508

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001390775	SCV001592616	pathogenic	not provided	2024-09-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln2404*) in the ZNF469 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1522 amino acid(s) of the ZNF469 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZNF469-related conditions. ClinVar contains an entry for this variant (Variation ID: 1076777). This variant disrupts a region of the ZNF469 protein in which other variant(s) (p.Glu2944Glyfs*50) have been determined to be pathogenic (PMID: 23010198). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001390775	SCV005325693	likely pathogenic	not provided	2024-03-06	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Nonsense variant predicted to result in protein truncation, as the last 1522 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24077912)