Submissions for variant NM_012193.4(FZD4):c.1282_1285del (p.Asp428fs)

dbSNP: rs80358295

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598865	SCV000709807	pathogenic	not provided	2022-08-12	criteria provided, single submitter	clinical testing	Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 110 amino acids are lost and replaced with one incorrect amino acid; This variant is associated with the following publications: (PMID: 20340138, 28494495, 30097784, 31827910, 31987760, 31299183, 33090715, 32238352, 33302760, 30452590)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000598865	SCV002235126	pathogenic	not provided	2025-01-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asp428Serfs*2) in the FZD4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 110 amino acid(s) of the FZD4 protein. This variant is present in population databases (rs80358295, gnomAD 0.008%). This premature translational stop signal has been observed in individual(s) with familial exudative vitreoretinopathy (PMID: 20340138, 28494495, 30452590). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 224625). For these reasons, this variant has been classified as Pathogenic.
3billion, Medical Genetics	RCV002250600	SCV002520949	likely pathogenic	Exudative vitreoretinopathy 1	2022-05-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by more than 10%. The variant has been reported to be associated with FZD4 related disorder (ClinVar ID: VCV000224625 / PMID: 20340138). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Revvity Omics, Revvity	RCV002250600	SCV003824543	pathogenic	Exudative vitreoretinopathy 1	2022-09-28	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816357	SCV005070829	pathogenic	Retinal dystrophy	2017-01-01	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000598865	SCV005198306	pathogenic	not provided	2024-03-08	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV002250600	SCV005200770	pathogenic	Exudative vitreoretinopathy 1	2024-05-08	criteria provided, single submitter	clinical testing	PVS1, PS2, PM6
Laboratory of Human Molecular Genetics, Department of Medical Research, Taipei Veterans General Hospital	RCV000210225	SCV000266328	pathogenic	Exudative retinopathy; Familial exudative vitreoretinopathy		no assertion criteria provided	research