NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter) AND Usher syndrome type 2A

Germline classification:: Pathogenic (11 submissions)
Last evaluated:: Nov 4, 2023
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:: RCV000002451.26

Allele description [Variation Report for NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)]

NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.11864G>A (p.Trp3955Ter)

HGVS:

NC_000001.11:g.215728232C>T
NG_009497.2:g.700217G>A
NM_206933.4:c.11864G>AMANE SELECT
NP_996816.3:p.Trp3955Ter
NC_000001.10:g.215901574C>T
NG_009497.1:g.700165G>A
NM_206933.2:c.11864G>A
NM_206933.3:c.11864G>A
c.11864G>A
p.Trp3955X

Protein change:

W3955*; TRP3955TER

Links:

OMIM: 608400.0007; dbSNP: rs111033364

NCBI 1000 Genomes Browser:

rs111033364

Molecular consequence:

NM_206933.4:c.11864G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Usher syndrome type 2A
Synonyms:: USHER SYNDROME, TYPE IIA; RETINAL DISEASE IN USHER SYNDROME TYPE IIA, MODIFIER OF
Identifiers:: MONDO: MONDO:0010169; MedGen: C1848634; Orphanet: 231178; Orphanet: 886; OMIM: 276901

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000022609	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2004)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001162877	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001194132	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2019))	Pathogenic (Dec 26, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001366417	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 21, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001451982	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV002556531	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 11, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002577544	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002581855	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002756439	The Shared Resource Centre "Genome", Research Centre for Medical Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 10, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004099463	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	no assertion criteria provided	Pathogenic (Oct 30, 2023)	germline	clinical testing
SCV004182064	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 4, 2023)	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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	8	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.

van Wijk E, Pennings RJ, te Brinke H, Claassen A, Yntema HG, Hoefsloot LH, Cremers FP, Cremers CW, Kremer H.

Am J Hum Genet. 2004 Apr;74(4):738-44. Epub 2004 Mar 10.

PubMed [citation]

PMID:: 15015129
PMCID:: PMC1181950

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

Bonnet C, Riahi Z, Chantot-Bastaraud S, Smagghe L, Letexier M, Marcaillou C, Lefèvre GM, Hardelin JP, El-Amraoui A, Singh-Estivalet A, Mohand-Saïd S, Kohl S, Kurtenbach A, Sliesoraityte I, Zobor D, Gherbi S, Testa F, Simonelli F, Banfi S, Fakin A, Glavač D, Jarc-Vidmar M, et al.

Eur J Hum Genet. 2016 Dec;24(12):1730-1738. doi: 10.1038/ejhg.2016.99. Epub 2016 Jul 27.

PubMed [citation]

PMID:: 27460420
PMCID:: PMC5117943

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000022609.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 patients with Usher syndrome type IIa (USH2A; 276901), van Wijk et al. (2004) found compound heterozygosity for a trp3955-to-ter (W3955X) mutation in the USH2A gene and 2 different mutations: a 949C-A transversion in one patient, resulting in an arg317-to-arg mutation (R317R; 608400.0008), which was predicted to create an additional 5-prime splice site in exon 5; and a 1256G-T transversion, resulting in a cys419-to-phe substitution (C419F; 608400.0009) in the second patient.

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

From Baylor Genetics, SCV001162877.1

#	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 Myriad Genetics, Inc., SCV001194132.2

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

Description

NM_206933.2(USH2A):c.11864G>A(W3955*) is classified as pathogenic in the context of USH2A-related disorders. Sources cited for classification include the following: PMID 27460420. Classification of NM_206933.2(USH2A):c.11864G>A(W3955*) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.

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

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001366417.2

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

Description

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2.

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

From Natera, Inc., SCV001451982.1

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

#	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 Genetics and Molecular Pathology, SA Pathology, SCV002556531.2

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV002577544.1

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

Description

PVS1, PM2, PP3, PP5

#	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

From MGZ Medical Genetics Center, SCV002581855.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From The Shared Resource Centre "Genome", Research Centre for Medical Genetics, SCV002756439.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	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	yes	not provided	not provided	not provided		6	not provided	not provided	not provided

From Zotz-Klimas Genetics Lab, MVZ Zotz Klimas, SCV004099463.1

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

#	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

From Genome-Nilou Lab, SCV004182064.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 26, 2024

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