NM_003468.4(FZD5):c.1081_1082insGAA (p.His361delinsArgAsn) AND Congenital ocular coloboma

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 18, 2019
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:: RCV001089478.1

Allele description [Variation Report for NM_003468.4(FZD5):c.1081_1082insGAA (p.His361delinsArgAsn)]

NM_003468.4(FZD5):c.1081_1082insGAA (p.His361delinsArgAsn)

Gene:

FZD5:frizzled class receptor 5 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

2q33.3

Genomic location:

Preferred name:

NM_003468.4(FZD5):c.1081_1082insGAA (p.His361delinsArgAsn)

HGVS:

NC_000002.12:g.207767658_207767659insTTC
NG_050642.1:g.6761_6762insGAA
NM_003468.4:c.1081_1082insGAAMANE SELECT
NP_003459.2:p.His361delinsArgAsn
NC_000002.11:g.208632382_208632383insTTC

Links:

dbSNP: rs2091987023

NCBI 1000 Genomes Browser:

rs2091987023

Molecular consequence:

NM_003468.4:c.1081_1082insGAA - inframe_indel - [Sequence Ontology: SO:0001820]

Observations:

Condition(s)

Name:: Congenital ocular coloboma
Synonyms:: COLOBOMA OF IRIS, CHOROID, AND RETINA; COLOBOMA, UVEORETINAL; Coloboma of eye; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0001476; MedGen: C0009363; Orphanet: 194; Human Phenotype Ontology: HP:0000589

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000998821	Genetics Department, University Hospital of Toulouse	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 18, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26908622, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000998821

Genetics Department, University Hospital of Toulouse

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 18, 2019)

germline

clinical testing

PubMed (2)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A secreted WNT-ligand-binding domain of FZD5 generated by a frameshift mutation causes autosomal dominant coloboma.

Liu C, Widen SA, Williamson KA, Ratnapriya R, Gerth-Kahlert C, Rainger J, Alur RP, Strachan E, Manjunath SH, Balakrishnan A, Floyd JA; UK10K Consortium., Li T, Waskiewicz A, Brooks BP, Lehmann OJ, FitzPatrick DR, Swaroop A.

Hum Mol Genet. 2016 Apr 1;25(7):1382-91. doi: 10.1093/hmg/ddw020. Epub 2016 Jan 24.

PubMed [citation]

PMID:: 26908622
PMCID:: PMC4787907

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 Genetics Department, University Hospital of Toulouse, SCV000998821.1

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

Description

This sequence change alteres a highly conserved amino acid (p.His361delinsArgAsn) in a major functional domain (frizzled domain) of the FZD5 gene. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FZD5-related disease. The loss of the Histidine with the insertion of two novel amino acids Arginine and Asparagine is predicted to be damaging on splicing by in silico analyses (Human Splicing Finder, GeneSplicer, ESEfinder).

#	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		1	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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