Submissions for variant NM_001367624.2(ZNF469):c.8344C>T (p.His2782Tyr)

gnomAD frequency: 0.00051  dbSNP: rs553227769

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000282615	SCV000399411	uncertain significance	Brittle cornea syndrome 1	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000658754	SCV000573346	uncertain significance	not provided	2024-11-08	criteria provided, single submitter	clinical testing	Not reported in individuals affected with a ZNF469-related phenotype to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29228253)
CeGaT Center for Human Genetics Tuebingen	RCV000658754	SCV000780544	uncertain significance	not provided	2021-03-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000658754	SCV002255047	uncertain significance	not provided	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 2754 of the ZNF469 protein (p.His2754Tyr). This variant is present in population databases (rs553227769, gnomAD 0.06%). 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: 320986). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002429275	SCV002681433	benign	Cardiovascular phenotype	2023-11-15	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000282615	SCV003920634	uncertain significance	Brittle cornea syndrome 1	2022-04-07	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in 0.1% (65/68034) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-88435814-C-T?dataset=gnomad_r3) and in ClinVar (Variation ID:320986). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000658754	SCV001809128	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000658754	SCV001974842	likely benign	not provided		no assertion criteria provided	clinical testing