rs72817951

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022124.6(CDH23):c.3370-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,552,824 control chromosomes in the GnomAD database, including 3,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene CDH23 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.047 ( 232 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3453 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.37

Publications

4 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 links:

C10orf105 (HGNC:20304): (chromosome 10 open reading frame 105) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C10orf105 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_022124.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for CDH23 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 10-71724016-G-A is Benign according to our data. Variant chr10-71724016-G-A is described in ClinVar as Benign. ClinVar VariationId is 261547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH23	NM_022124.6	MANE Select	c.3370-29G>A	intron	N/A	NP_071407.4
CDH23	NM_001171930.2		c.3370-29G>A	intron	N/A	NP_001165401.1	A0A087WYR8
C10orf105	NM_001168390.2		c.-5-7674C>T	intron	N/A	NP_001161862.1	Q8TEF2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CDH23	ENST00000224721.12	TSL:5 MANE Select	c.3370-29G>A	intron	N/A	ENSP00000224721.9	Q9H251-1
CDH23	ENST00000616684.4	TSL:5	c.3370-29G>A	intron	N/A	ENSP00000482036.2	A0A087WYR8
CDH23	ENST00000398809.9	TSL:5	c.3374-36G>A	intron	N/A	ENSP00000381789.5	A0A0A0MS94

Frequencies

GnomAD3 genomes

AF:

0.0471

AC:

7171

AN:

152200

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0442

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.0681

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0742

Gnomad OTH

AF:

0.0521

GnomAD2 exomes

AF:

0.0441

AC:

6924

AN:

156900

AF XY:

0.0429

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.0312

Gnomad ASJ exome

AF:

0.0282

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0656

Gnomad NFE exome

AF:

0.0713

Gnomad OTH exome

AF:

0.0512

GnomAD4 exome

AF:

0.0658

AC:

92142

AN:

1400506

Hom.:

3453

Cov.:

AF XY:

0.0639

AC XY:

44177

AN XY:

690910

show subpopulations

African (AFR)

AF:

0.0106

AC:

335

AN:

31692

American (AMR)

AF:

0.0337

AC:

1207

AN:

35842

Ashkenazi Jewish (ASJ)

AF:

0.0255

AC:

642

AN:

25192

East Asian (EAS)

AF:

0.0000557

AC:

AN:

35898

South Asian (SAS)

AF:

0.00782

AC:

620

AN:

79282

European-Finnish (FIN)

AF:

0.0638

AC:

3150

AN:

49350

Middle Eastern (MID)

AF:

0.00860

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0766

AC:

82733

AN:

1079468

Other (OTH)

AF:

0.0586

AC:

3404

AN:

58084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

4763

9526

14290

19053

23816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3028

6056

9084

12112

15140

<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:

0.0471

AC:

7169

AN:

152318

Hom.:

232

Cov.:

AF XY:

0.0451

AC XY:

3358

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0118

AC:

491

AN:

41558

American (AMR)

AF:

0.0441

AC:

675

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00849

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0681

AC:

723

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0742

AC:

5050

AN:

68016

Other (OTH)

AF:

0.0510

AC:

108

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

365

731

1096

1462

1827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0447

Hom.:

Bravo

AF:

0.0438

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.1

(source)

DANN

Benign

0.84

PhyloP100

1.4

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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