Submissions for variant NM_001367624.2(ZNF469):c.5914G>A (p.Gly1972Arg)

gnomAD frequency: 0.00019  dbSNP: rs766410344

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413617	SCV000492437	uncertain significance	not specified	2016-12-15	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the ZNF469 gene. The G1944R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 2,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, but was observed in 17/7004 (0.24%) alleles from individuals of Non-Finnish European ancestry in the Exome Aggregation Consortium. The G1944R 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. However, this substitution occurs at a position that is not conserved across species and in silico analysis predicts this variant likely does not alter the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Fulgent Genetics, Fulgent Genetics	RCV000764089	SCV000895053	uncertain significance	Brittle cornea syndrome 1	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002058871	SCV002415484	likely benign	not provided	2024-11-27	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278649	SCV002565374	likely benign	Ehlers-Danlos syndrome	2020-12-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002356512	SCV002649866	likely benign	Cardiovascular phenotype	2020-03-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV002058871	SCV004138074	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	ZNF469: BP4
PreventionGenetics, part of Exact Sciences	RCV003950323	SCV004764063	likely benign	ZNF469-related disorder	2019-11-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).