NM_206933.4(USH2A):c.5516T>A (p.Val1839Glu) AND not provided

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

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Aug 29, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV001240204.17

Allele description

NM_206933.4(USH2A):c.5516T>A (p.Val1839Glu)

Genes:

USH2A-AS2:USH2A antisense RNA 2 [Gene - HGNC]
USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.5516T>A (p.Val1839Glu)

HGVS:

NC_000001.11:g.216078145A>T
NG_009497.2:g.350304T>A
NM_206933.4:c.5516T>AMANE SELECT
NP_996816.3:p.Val1839Glu
NC_000001.10:g.216251487A>T
NG_009497.1:g.350252T>A
NM_206933.1:c.5516T>A
NM_206933.2:c.5516T>A
NM_206933.3(USH2A):c.5516T>A
p.Val1839Glu

Protein change:

V1839E

Links:

dbSNP: rs886039867

NCBI 1000 Genomes Browser:

rs886039867

Molecular consequence:

NM_206933.4:c.5516T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Synthetic construct Homo sapiens cDNA clone IMAGE:3939141, **** WARNING: chimeric clone ****
gi|13325447|gb|BC004521.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001413130	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 29, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26927203, 28224992, 28944237, 28492532
SCV001920648	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001973482	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV004125616	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Aug 1, 2022)	germline	clinical testing	Citation Link

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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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa.

Pierrache LH, Hartel BP, van Wijk E, Meester-Smoor MA, Cremers FP, de Baere E, de Zaeytijd J, van Schooneveld MJ, Cremers CW, Dagnelie G, Hoyng CB, Bergen AA, Leroy BP, Pennings RJ, van den Born LI, Klaver CC.

Ophthalmology. 2016 May;123(5):1151-60. doi: 10.1016/j.ophtha.2016.01.021. Epub 2016 Feb 27.

PubMed [citation]

PMID:: 26927203

Diagnostic exome sequencing in 266 Dutch patients with visual impairment.

Haer-Wigman L, van Zelst-Stams WA, Pfundt R, van den Born LI, Klaver CC, Verheij JB, Hoyng CB, Breuning MH, Boon CJ, Kievit AJ, Verhoeven VJ, Pott JW, Sallevelt SC, van Hagen JM, Plomp AS, Kroes HY, Lelieveld SH, Hehir-Kwa JY, Castelein S, Nelen M, Scheffer H, Lugtenberg D, et al.

Eur J Hum Genet. 2017 May;25(5):591-599. doi: 10.1038/ejhg.2017.9. Epub 2017 Feb 22.

PubMed [citation]

PMID:: 28224992
PMCID:: PMC5437915

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001413130.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This missense change has been observed in individual(s) with clinical features of USH2A-related conditions and/or clinical features of Usher syndrome (PMID: 26927203, 28224992, 28944237; Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 265979). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1839 of the USH2A protein (p.Val1839Glu).

#	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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001920648.1

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001973482.1

#	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 CeGaT Center for Human Genetics Tuebingen, SCV004125616.6

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

Description

USH2A: PM2, PP1

#	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: Jun 23, 2024

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