rs10999978

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_022124.6(CDH23):c.4509C>T(p.Gly1503Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,613,720 control chromosomes in the GnomAD database, including 2,099 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 340 hom., cov: 33)

Exomes 𝑓: 0.017 ( 1759 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.504

Publications

8 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
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Usher syndrome type 1D
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Usher syndrome type 1
Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CDH23 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 10-71740842-C-T is Benign according to our data. Variant chr10-71740842-C-T is described in ClinVar as Benign. ClinVar VariationId is 45949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.504 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022124.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	NM_022124.6	MANE Select	c.4509C>T	p.Gly1503Gly	synonymous	Exon 37 of 70	NP_071407.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.4509C>T	p.Gly1503Gly	synonymous	Exon 37 of 70	ENSP00000224721.9	Q9H251-1
	CDH23	ENST00000398792.3	TSL:2	n.1198C>T		non_coding_transcript_exon	Exon 8 of 9

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6229

AN:

152188

Hom.:

339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.0221

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0487

AC:

12127

AN:

248956

AF XY:

0.0406

show subpopulations

Gnomad AFR exome

AF:

0.0733

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.0178

Gnomad EAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.00308

Gnomad OTH exome

AF:

0.0373

GnomAD4 exome

AF:

0.0169

AC:

24731

AN:

1461414

Hom.:

1759

Cov.:

AF XY:

0.0162

AC XY:

11793

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.0731

AC:

2449

AN:

33480

American (AMR)

AF:

0.169

AC:

7563

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0169

AC:

441

AN:

26134

East Asian (EAS)

AF:

0.202

AC:

8019

AN:

39692

South Asian (SAS)

AF:

0.0248

AC:

2138

AN:

86258

European-Finnish (FIN)

AF:

0.0112

AC:

594

AN:

53148

Middle Eastern (MID)

AF:

0.0295

AC:

170

AN:

5768

European-Non Finnish (NFE)

AF:

0.00160

AC:

1783

AN:

1111846

Other (OTH)

AF:

0.0261

AC:

1574

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1130

2259

3389

4518

5648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

350

700

1050

1400

1750

<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:

0.0410

AC:

6243

AN:

152306

Hom.:

340

Cov.:

AF XY:

0.0432

AC XY:

3217

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0726

AC:

3016

AN:

41554

American (AMR)

AF:

0.110

AC:

1691

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

991

AN:

5166

South Asian (SAS)

AF:

0.0222

AC:

107

AN:

4830

European-Finnish (FIN)

AF:

0.0119

AC:

126

AN:

10618

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00254

AC:

173

AN:

68034

Other (OTH)

AF:

0.0416

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

294

589

883

1178

1472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0192

Hom.:

684

Bravo

AF:

0.0530

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00433

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Autosomal recessive nonsyndromic hearing loss 12 (1)

Usher syndrome type 1 (1)

Usher syndrome type 1D (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

7.8

(source)

DANN

Benign

0.82

PhyloP100

0.50

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over