NM_012193.4(FZD4):c.1282_1285del (p.Asp428fs) AND Exudative vitreoretinopathy 1

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: May 8, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002250600.5

Allele description [Variation Report for NM_012193.4(FZD4):c.1282_1285del (p.Asp428fs)]

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

Genes:

FZD4:frizzled class receptor 4 [Gene - OMIM - HGNC]
PRSS23:serine protease 23 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

11q14.2

Genomic location:

Preferred name:

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

HGVS:

NC_000011.10:g.86951472GTCT[1]
NG_011752.1:g.8914GACA[1]
NM_012193.4:c.1282_1285delMANE SELECT
NP_036325.2:p.Asp428fs
NC_000011.9:g.86662513_86662516del
NC_000011.9:g.86662514GTCT[1]
NM_012193.3:c.1282_1285del
NM_012193.3:c.1282_1285delGACA
NR_120591.3:n.835GTCT[1]
NR_120592.2:n.584GTCT[1]

Protein change:

D428fs

Links:

dbSNP: rs80358295

NCBI 1000 Genomes Browser:

rs80358295

Molecular consequence:

NM_012193.4:c.1282_1285del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_120591.3:n.835GTCT[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_120592.2:n.584GTCT[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Exudative vitreoretinopathy 1 (EVR1)
Synonyms:: Criswick-Schepens syndrome; FEVR, AUTOSOMAL DOMINANT; Familial exudative vitreoretinopathy, autosomal dominant
Identifiers:: MONDO: MONDO:0007589; MedGen: C1851402; Orphanet: 891; Orphanet: 90050; OMIM: 133780

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002520949	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20340138, 25741868
SCV003824543	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 28, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005200770	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 8, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002520949

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 22, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003824543

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 28, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV005200770

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 8, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP.

Nikopoulos K, Venselaar H, Collin RW, Riveiro-Alvarez R, Boonstra FN, Hooymans JM, Mukhopadhyay A, Shears D, van Bers M, de Wijs IJ, van Essen AJ, Sijmons RH, Tilanus MA, van Nouhuys CE, Ayuso C, Hoefsloot LH, Cremers FP.

Hum Mutat. 2010 Jun;31(6):656-66. doi: 10.1002/humu.21250.

PubMed [citation]

PMID:: 20340138

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002520949.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003824543.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV005200770.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

PVS1, PS2, PM6

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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