U.S. flag

An official website of the United States government

NM_206933.4(USH2A):c.5776+1G>A AND Rare genetic deafness

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 2, 2015
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:
RCV000213465.5

Allele description [Variation Report for NM_206933.4(USH2A):c.5776+1G>A]

NM_206933.4(USH2A):c.5776+1G>A

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.5776+1G>A
Other names:
p.p.(=)
HGVS:
  • NC_000001.11:g.216073096C>T
  • NG_009497.2:g.355353G>A
  • NM_206933.4:c.5776+1G>AMANE SELECT
  • NC_000001.10:g.216246438C>T
  • NM_206933.2:c.5776+1G>A
  • NM_206933.3:c.5776+1G>A
Links:
dbSNP: rs876657731
NCBI 1000 Genomes Browser:
rs876657731
Molecular consequence:
  • NM_206933.4:c.5776+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
2

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: C5680250; Orphanet: 96210

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000271472Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Apr 2, 2015) 		germlineclinical testing

PubMed (10)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing

Citations

PubMed

Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis.

Lenarduzzi S, Vozzi D, Morgan A, Rubinato E, D'Eustacchio A, Osland TM, Rossi C, Graziano C, Castorina P, Ambrosetti U, Morgutti M, Girotto G.

Hear Res. 2015 Feb;320:18-23. doi: 10.1016/j.heares.2014.12.006. Epub 2015 Jan 6.

PubMed [citation]
PMID:
25575603

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Lenassi E, Vincent A, Li Z, Saihan Z, Coffey AJ, Steele-Stallard HB, Moore AT, Steel KP, Luxon LM, Héon E, Bitner-Glindzicz M, Webster AR.

Eur J Hum Genet. 2015 Oct;23(10):1318-27. doi: 10.1038/ejhg.2014.283. Epub 2015 Feb 4.

PubMed [citation]
PMID:
25649381
PMCID:
PMC4592079
See all PubMed Citations (10)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271472.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (10)

Description

The c.5776+1G>A variant in USH2A has been previously reported in 12 individuals: 9 with Usher syndrome and 2 with retinitis pigmentosa (Baux 2014, Dreyer 2008, Glockle 2014, Jaijo 2010, Lenarduzzi 2015, Lenassi 2015, Sandberg 2008, Sodi 201 4, Wang 2014). Ten of these individuals were either compound heterozygous or hom ozygous for the variant. This variant has not been reported in large population studies. The c.5776+1G>A variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Furthermore, analysis of mRNA extracted from a c arrier of the c.5776+1G>A variant showed in-frame skipping of exon 28 (Lenassi 2 015), confirming a splicing impact. In summary, this variant meets our criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive mann er (www.partners.org/personalizedmedicine/lmm) based upon its identification in the homozygous or compound heterozygous state in multiple affected individuals a nd the reported impact on splicing.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

Last Updated: Apr 15, 2024