Submissions for variant NM_001367624.2(ZNF469):c.8503G>C (p.Glu2835Gln)

gnomAD frequency: 0.00073  dbSNP: rs200153921

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000304531	SCV000399414	uncertain significance	Brittle cornea syndrome 1	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001712037	SCV000532890	benign	not provided	2020-02-27	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000304531	SCV002496041	uncertain significance	Brittle cornea syndrome 1	2021-03-30	criteria provided, single submitter	clinical testing	ZNF469 NM_001127464.2 p.Glu2807Gln (c.8419G>C): This variant has not been reported in the literature but is present in 0.1% (69/68040) of European alleles, in addition to 1 South Asian homozygote, in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/rs200153921?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID: 320989). This variant amino acid Glutamine (Gln) is present in several species including multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278472	SCV002565423	likely benign	Ehlers-Danlos syndrome	2021-07-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002411216	SCV002675815	likely benign	Cardiovascular phenotype	2022-05-31	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.
Invitae	RCV001712037	SCV003251514	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001712037	SCV004033506	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	ZNF469: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003972372	SCV004790249	likely benign	ZNF469-related disorder	2021-09-30	criteria provided, single submitter	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).