10-71439744-C-A

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.-5-83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 960,604 control chromosomes in the GnomAD database, including 101,347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 12204 hom., cov: 33)

Exomes 𝑓: 0.46 ( 89143 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.127

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, 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 10-71439744-C-A is Benign according to our data. Variant chr10-71439744-C-A is described in ClinVar as [Benign]. Clinvar id is 670320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.-5-83C>A		intron_variant	Intron 1 of 69	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.-5-83C>A		intron_variant	Intron 1 of 69	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54646

AN:

152050

Hom.:

12205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0896

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.356

GnomAD4 exome

AF:

0.461

AC:

372774

AN:

808436

Hom.:

89143

AF XY:

0.458

AC XY:

189945

AN XY:

414362

show subpopulations

African (AFR)

AF:

0.0858

AC:

1616

AN:

18830

American (AMR)

AF:

0.381

AC:

12458

AN:

32706

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

7656

AN:

19514

East Asian (EAS)

AF:

0.551

AC:

18129

AN:

32900

South Asian (SAS)

AF:

0.367

AC:

22885

AN:

62302

European-Finnish (FIN)

AF:

0.503

AC:

23107

AN:

45894

Middle Eastern (MID)

AF:

0.311

AC:

1387

AN:

4458

European-Non Finnish (NFE)

AF:

0.486

AC:

269143

AN:

553500

Other (OTH)

AF:

0.428

AC:

16393

AN:

38332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9937

19874

29812

39749

49686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.359

AC:

54641

AN:

152168

Hom.:

12204

Cov.:

AF XY:

0.362

AC XY:

26902

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.0894

AC:

3715

AN:

41556

American (AMR)

AF:

0.379

AC:

5796

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1342

AN:

3468

East Asian (EAS)

AF:

0.505

AC:

2603

AN:

5158

South Asian (SAS)

AF:

0.359

AC:

1733

AN:

4828

European-Finnish (FIN)

AF:

0.519

AC:

5499

AN:

10602

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.480

AC:

32633

AN:

67956

Other (OTH)

AF:

0.354

AC:

746

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1581

3161

4742

6322

7903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.325

Hom.:

1389

Bravo

AF:

0.339

Asia WGS

AF:

0.334

AC:

1161

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

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. -

Usher syndrome type 1D

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.1

(source)

DANN

Benign

0.80

PhyloP100

-0.13

PromoterAI

-0.040

Neutral

(source)

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

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10-71439744-C-A

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