NM_206933.4(USH2A):c.1256G>T (p.Cys419Phe) AND USH2A-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 28, 2017
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:: RCV000778222.6

Allele description [Variation Report for NM_206933.4(USH2A):c.1256G>T (p.Cys419Phe)]

NM_206933.4(USH2A):c.1256G>T (p.Cys419Phe)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.1256G>T (p.Cys419Phe)

HGVS:

NC_000001.11:g.216324240C>A
NG_009497.2:g.104209G>T
NM_007123.6:c.1256G>T
NM_206933.4:c.1256G>TMANE SELECT
NP_009054.5:p.Cys419Phe
NP_009054.6:p.Cys419Phe
NP_996816.3:p.Cys419Phe
NC_000001.10:g.216497582C>A
NG_009497.1:g.104157G>T
NM_007123.5:c.1256G>T
NM_206933.2:c.1256G>T
NM_206933.3:c.1256G>T
O75445:p.Cys419Phe
c.1256G>T

Protein change:

C419F; CYS419PHE

Links:

UniProtKB: O75445#VAR_025767; OMIM: 608400.0009; dbSNP: rs121912600

NCBI 1000 Genomes Browser:

rs121912600

Molecular consequence:

NM_007123.6:c.1256G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_206933.4:c.1256G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: USH2A-related disorder
Synonyms:: USH2A-Related Disorders; USH2A-related condition
Identifiers:: MedGen: CN239332

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RecName: Full=Solute carrier family 2, facilitated glucose transporter member 3; AltName: Full=Glucose transporter type 3, brain; Short=GLUT-3
gi|121760|sp|P11169.1|GTR3_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000914388	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (Apr 28, 2017)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 16963483, 10729113, 15015129, 15325563, 18641288, 22334370, 22135276, 24265693, 24498627, 15241801, 25999674 Citation Link,
SCV001251480	UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill - NSIGHT-NC NEXUS	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	paternal	research	PubMed (9) [See all records that cite these PMIDs] 20301515, 15015129, 15241801, 15325563, 10729113, 22135276, 24944099, 25999674, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000914388

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Pathogenic
(Apr 28, 2017)

germline

clinical testing

PubMed (11)
[See all records that cite these PMIDs]

Citation Link,

SCV001251480

UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill - NSIGHT-NC NEXUS

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

paternal

research

PubMed (9)
[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
not provided	paternal	yes	1	not provided	not provided	not provided	not provided	research

Citations

PubMed

Development of a genotyping microarray for Usher syndrome.

Cremers FP, Kimberling WJ, Külm M, de Brouwer AP, van Wijk E, te Brinke H, Cremers CW, Hoefsloot LH, Banfi S, Simonelli F, Fleischhauer JC, Berger W, Kelley PM, Haralambous E, Bitner-Glindzicz M, Webster AR, Saihan Z, De Baere E, Leroy BP, Silvestri G, McKay GJ, Koenekoop RK, et al.

J Med Genet. 2007 Feb;44(2):153-60. Epub 2006 Sep 8.

PubMed [citation]

PMID:: 16963483
PMCID:: PMC2598068

Disease course in patients with autosomal recessive retinitis pigmentosa due to the USH2A gene.

Sandberg MA, Rosner B, Weigel-DiFranco C, McGee TL, Dryja TP, Berson EL.

Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5532-9. doi: 10.1167/iovs.08-2009. Epub 2008 Jul 18.

PubMed [citation]

PMID:: 18641288
PMCID:: PMC2588642

See all PubMed Citations (14)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000914388.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

Across a selection of the available literature, the USH2A c.1256G>T (p.Cys419Phe) missense variant has been identified in a homozygous state in two patients with Usher syndrome, in a compound heterozygous state in 13 patients of whom ten were diagnosed with Usher syndrome and three with retinitis pigmentosa (RP), and in a heterozygous state in 16 patients of whom ten were diagnosed with Usher syndrome and six with RP (Weston et al. 2000; Van Wijk et al. 2004; Seyedahmadi et al. 2004; Sandberg et al. 2008; Neveling et al. 2012; Le Quesne Stabe et al. 2012; Eisenberger et al. 2013; Besnard et al. 2014; Cremers et al. 2014; Pennings et al. 2004; Van Huet et al. 2015). The p.Cys419Phe variant is a possible Dutch founder variant as deduced by haplotype analysis by Pennings et al. (2004). The p.Cys419Phe variant was absent in at least 1000 controls and is reported at a frequency of 0.000093 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the collective evidence, the p.Cys419Phe variant is classified as pathogenic for USH2A-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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 UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill - NSIGHT-NC NEXUS, SCV001251480.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (9)

Description

USH2A c.1256G>T (p.C419F) has been described as a pathogenic variant and has been reported in the homozygous or compound heterozygous state in multiple individuals with Usher syndrome type IIA and nonsyndromic retinitis pigmentosa (PMID: 15015129; 15241801;15325563; 10729113; 22135276; 24944099; 25999674).

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

Last Updated: Oct 13, 2024

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