NM_022124.6(CDH23):c.6050-9G>A AND Rare genetic deafness

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 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:: RCV000039236.6

Allele description [Variation Report for NM_022124.6(CDH23):c.6050-9G>A]

NM_022124.6(CDH23):c.6050-9G>A

Gene:

CDH23:cadherin related 23 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_022124.6(CDH23):c.6050-9G>A

HGVS:

NC_000010.11:g.71791123G>A
NG_008835.1:g.399177G>A
NM_022124.6:c.6050-9G>AMANE SELECT
NC_000010.10:g.73550880G>A
NM_022124.5:c.6050-9G>A
c.6050-9G>A

Links:

dbSNP: rs367928692

NCBI 1000 Genomes Browser:

rs367928692

Molecular consequence:

NM_022124.6:c.6050-9G>A - intron variant - [Sequence Ontology: SO:0001627]

Observations:

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

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000062920	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Feb 3, 2015)	germline	clinical testing	PubMed (15) [See all records that cite these PMIDs] 12075507, 11857743, 18429043, 21569298, 21436283, 20513143, 19683999, 20613545, 25404053, 21940737, 24498627, 15353998, 16679490, 17407589, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000062920

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Feb 3, 2015)

germline

clinical testing

PubMed (15)
[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	not provided	6	3	not provided	not provided	not provided	clinical testing

Citations

PubMed

CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.

Astuto LM, Bork JM, Weston MD, Askew JW, Fields RR, Orten DJ, Ohliger SJ, Riazuddin S, Morell RJ, Khan S, Riazuddin S, Kremer H, van Hauwe P, Moller CG, Cremers CW, Ayuso C, Heckenlively JR, Rohrschneider K, Spandau U, Greenberg J, Ramesar R, Reardon W, et al.

Am J Hum Genet. 2002 Aug;71(2):262-75. Epub 2002 Jun 19.

PubMed [citation]

PMID:: 12075507
PMCID:: PMC379159

Identification and in vitro expression of novel CDH23 mutations of patients with Usher syndrome type 1D.

von Brederlow B, Bolz H, Janecke A, La O Cabrera A, Rudolph G, Lorenz B, Schwinger E, Gal A.

Hum Mutat. 2002 Mar;19(3):268-73.

PubMed [citation]

PMID:: 11857743

See all PubMed Citations (15)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000062920.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	PubMed (15)

Description

The c.6050-9G>A variant in CHD23 has been reported in >20 individuals with Usher syndrome who were homozygous or compound heterozygous for the variant. The vari ant segregated with disease in 3 affected relatives from 3 families (von Brederl ow 2002, Astuto 2002, Pennings 2004, Roux 2006, Ebermann 2007, Oshima 2008, Jaij o 2009, Vache 2010, Kimberling 2010, Bonnet 2011, Roux 2011, Schultz 2011, Besna rd 2014). This variant has been identified in 3/28260 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs36 7928692). Although this variant has been seen in the general population, its fre quency is low enough to be consistent with a recessive carrier frequency. This v ariant is located in the 3' splice region. In vitro functional studies provide e vidence that the c.6050-9G>A variant impacts splicing (Von Brederlow 2002, Vache 2010). In summary, this variant meets our criteria to be classified as pathogen ic for Usher syndrome in an autosomal recessive manner. ACMG/AMP codes applied: PM3_VeryStrong; PM2; PS3_Moderate; PP4.

#	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		6	not provided	3	not provided

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine