NM_022124.6(CDH23):c.6442G>A (p.Asp2148Asn) AND Autosomal recessive nonsyndromic hearing loss 12

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 3, 2018
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:: RCV000005204.11

Allele description [Variation Report for NM_022124.6(CDH23):c.6442G>A (p.Asp2148Asn)]

NM_022124.6(CDH23):c.6442G>A (p.Asp2148Asn)

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.6442G>A (p.Asp2148Asn)

HGVS:

NC_000010.11:g.71793370G>A
NG_008835.1:g.401424G>A
NM_022124.6:c.6442G>AMANE SELECT
NP_071407.4:p.Asp2148Asn
NC_000010.10:g.73553127G>A
NM_022124.5:c.6442G>A
c.6442G>A

Protein change:

D2148N; ASP2148ASN

Links:

OMIM: 605516.0008; dbSNP: rs111033271

NCBI 1000 Genomes Browser:

rs111033271

Molecular consequence:

NM_022124.6:c.6442G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 12
Synonyms:: Deafness, autosomal recessive 12
Identifiers:: MONDO: MONDO:0011067; MedGen: C1832394; Orphanet: 90636; OMIM: 601386

Recent activity

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hypothetical protein SERP2214 [Staphylococcus epidermidis RP62A]
hypothetical protein SERP2214 [Staphylococcus epidermidis RP62A]
gi|57636259|gnl|tigr|SE2214|gb|AAW5 1|

Protein
UI-H-EI1-ayx-o-19-0-UI.s1 NCI_CGAP_EI1 Homo sapiens cDNA clone IMAGE:5845098 3',...
UI-H-EI1-ayx-o-19-0-UI.s1 NCI_CGAP_EI1 Homo sapiens cDNA clone IMAGE:5845098 3', mRNA sequence
gi|19727936|gnl|dbEST|11843471|gb|B 36.1|

Nucleotide
CM1-TN0141-250900-439-a06 TN0141 Homo sapiens cDNA, mRNA sequence
CM1-TN0141-250900-439-a06 TN0141 Homo sapiens cDNA, mRNA sequence
gi|11339919|gnl|dbEST|6841911|gb|BF 4.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025381	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2003)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 12075507, 12522556, 2706105
SCV000363841	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (May 3, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 12075507, 21940737, 12522556 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025381

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2003)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

SCV000363841

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Pathogenic
(May 3, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Citations

PubMed

Autosomal recessive nonsyndromal profound childhood deafness in a large pedigree. Audiometric features of the affected persons and the obligate carriers.

Marres HA, Cremers CW.

Arch Otolaryngol Head Neck Surg. 1989 May;115(5):591-5.

PubMed [citation]

PMID:: 2706105

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

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000025381.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In 2 presumably unrelated families with autosomal recessive nonsyndromic deafness mapping to chromosome 10q (DFNB12; 601386), Astuto et al. (2002) found an asp2148-to-asn (D2148N) mutation in the CDH23 gene, located in exon 47 in extracellular domain 20.

De Brouwer et al. (2003) performed a genetic analysis of a large consanguineous family with DFNB12 that was previously described by Marres and Cremers (1989). Patients in 1 branch of the family were homozygous for the 35delG mutation in the GJB2 gene (121011.0005) causing DFNB1 (220290). Patients in 2 other branches carried 2 novel mutations in the CDH23 gene causing DFNB12: a homozygous 6442G-A transition in exon 47 causing the D2148N mutation in 1 branch, and compound heterozygosity for this mutation and a 4021G-A transition causing an asp1341-to-asn (D1341N) mutation (605516.0009).

#	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 Illumina Laboratory Services, Illumina, SCV000363841.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The CDH23 c.6442G>A (p.Asp2148Asn) missense variant has been reported in three studies in which it is found in a total of eight individuals with hearing loss, including in two in a homozygous state, in five in a compound heterozygous state, and in one where zygosity was not specified (Astuto et al. 2002; De Brouwer et al. 2003; Schultz et al. 2011). This variant was also identified in 14 unaffected individuals in a heterozygous state. The p.Asp2148Asn variant was absent from a total of 296 controls and is reported at a frequency of 0.00015 in the European (non-Finnish) population of Exome Aggregation Consortium. Protein modelling studies revealed the Asp2148 residue is conserved and located in a calcium binding domain. Other aspartic acid to asparagine substitions associated with disease have been reported in these domains (de Brouwer et al. 2003). Based on the evidence, the p.Asp2148Asn variant is classified as pathogenic for autosomal recessive nonsyndromic hearing loss. 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

Last Updated: Oct 13, 2024

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