NM_012193.4(FZD4):c.827del (p.Gly276fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 22, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002839440.2

Allele description

NM_012193.4(FZD4):c.827del (p.Gly276fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

11q14.2

Genomic location:

Preferred name:

NM_012193.4(FZD4):c.827del (p.Gly276fs)

HGVS:

NC_000011.10:g.86951930del
NG_011752.1:g.8463del
NG_011752.2:g.8466del
NM_012193.4:c.827delMANE SELECT
NP_036325.2:p.Gly276fs
NC_000011.9:g.86662971del
NC_000011.9:g.86662972del
NR_120591.3:n.1293del
NR_120592.2:n.1042del

Protein change:

G276fs

Molecular consequence:

NM_012193.4:c.827del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_120591.3:n.1293del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_120592.2:n.1042del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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protein MTSS 1 isoform 8 [Mus musculus]
protein MTSS 1 isoform 8 [Mus musculus]
gi|2214681105|ref|NP_001390432.1|

Protein
PREDICTED: Mus musculus MTSS I-BAR domain containing 1 (Mtss1), transcript varia...
PREDICTED: Mus musculus MTSS I-BAR domain containing 1 (Mtss1), transcript variant X14, mRNA
gi|1907111265|ref|XM_017316531.3|

Nucleotide
protein MTSS 1 isoform X16 [Mus musculus]
protein MTSS 1 isoform X16 [Mus musculus]
gi|1720383822|ref|XP_030104306.1|

Protein
protein MTSS 1 isoform 1 [Mus musculus]
protein MTSS 1 isoform 1 [Mus musculus]
gi|226052002|ref|NP_659049.2|

Protein
Mus musculus BAC clone RP23-320F5 from chromosome 15, complete sequence
Mus musculus BAC clone RP23-320F5 from chromosome 15, complete sequence
gi|62198443|gb|AC130823.4||gnl|wugs 3-320F5

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003219515	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15223780, 23077402, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003219515

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 22, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Spectrum and frequency of FZD4 mutations in familial exudative vitreoretinopathy.

Toomes C, Bottomley HM, Scott S, Mackey DA, Craig JE, Appukuttan B, Stout JT, Flaxel CJ, Zhang K, Black GC, Fryer A, Downey LM, Inglehearn CF.

Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2083-90.

PubMed [citation]

PMID:: 15223780

Identification of FZD4 and LRP5 mutations in 11 of 49 families with familial exudative vitreoretinopathy.

Yang H, Li S, Xiao X, Wang P, Guo X, Zhang Q.

Mol Vis. 2012;18:2438-46. Epub 2012 Oct 4.

PubMed [citation]

PMID:: 23077402
PMCID:: PMC3472927

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003219515.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FZD4 protein in which other variant(s) (p.Gln505*) have been determined to be pathogenic (PMID: 15223780, 23077402). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with FZD4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly276Alafs*29) in the FZD4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 262 amino acid(s) of the FZD4 protein.

#	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

Last Updated: Feb 20, 2024

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