rs10762480

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022124.6(CDH23):c.5100C>T(p.Tyr1700Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,613,522 control chromosomes in the GnomAD database, including 33,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 2975 hom., cov: 31)

Exomes 𝑓: 0.20 ( 30630 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.91

Publications

19 publications found

Variant links:

Genes affected

CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]

CDH23 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 12
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 1D
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CDH23 links:

ENSG00000306531 (HGNC:):

ENSG00000306531 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 10-71778221-C-T is Benign according to our data. Variant chr10-71778221-C-T is described in ClinVar as Benign. ClinVar VariationId is 45965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.5100C>T	p.Tyr1700Tyr	synonymous_variant	Exon 40 of 70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDH23	ENST00000224721.12 link	c.5100C>T	p.Tyr1700Tyr	synonymous_variant	Exon 40 of 70	5	NM_022124.6	ENSP00000224721.9	Q9H251-1
ENSG00000306531	ENST00000819235.1 link	n.158-1156G>A		intron_variant	Intron 1 of 1
ENSG00000306531	ENST00000819236.1 link	n.157-1053G>A		intron_variant	Intron 1 of 1
ENSG00000306531	ENST00000819237.1 link	n.146-1151G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29786

AN:

151806

Hom.:

2972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.188

GnomAD2 exomes

AF:

0.187

AC:

46533

AN:

249136

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.202

AC:

295842

AN:

1461598

Hom.:

30630

Cov.:

AF XY:

0.200

AC XY:

145667

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.188

AC:

6309

AN:

33472

American (AMR)

AF:

0.126

AC:

5644

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

4446

AN:

26136

East Asian (EAS)

AF:

0.220

AC:

8731

AN:

39698

South Asian (SAS)

AF:

0.142

AC:

12264

AN:

86254

European-Finnish (FIN)

AF:

0.238

AC:

12726

AN:

53390

Middle Eastern (MID)

AF:

0.140

AC:

809

AN:

5764

European-Non Finnish (NFE)

AF:

0.210

AC:

233180

AN:

1111796

Other (OTH)

AF:

0.194

AC:

11733

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

13624

27248

40873

54497

68121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8026

16052

24078

32104

40130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.196

AC:

29796

AN:

151924

Hom.:

2975

Cov.:

AF XY:

0.196

AC XY:

14558

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.189

AC:

7845

AN:

41410

American (AMR)

AF:

0.158

AC:

2421

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

582

AN:

3470

East Asian (EAS)

AF:

0.201

AC:

1037

AN:

5150

South Asian (SAS)

AF:

0.145

AC:

696

AN:

4810

European-Finnish (FIN)

AF:

0.249

AC:

2623

AN:

10538

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

14016

AN:

67952

Other (OTH)

AF:

0.186

AC:

393

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1248

2496

3743

4991

6239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.204

Hom.:

1754

Bravo

AF:

0.188

Asia WGS

AF:

0.156

AC:

541

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jul 08, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 07, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jun 12, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1D

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.95

(source)

DANN

Benign

0.82

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over