NM_022124.6:c.-35_-31dupAGGCG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_022124.6(CDH23):c.-35_-31dupAGGCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 13441 hom., cov: 0)

Exomes 𝑓: 0.40 ( 2201 hom. )

Consequence

CDH23
NM_022124.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0300

Publications

2 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 -16 ACMG points.

BP6

Variant 10-71397276-C-CCGAGG is Benign according to our data. Variant chr10-71397276-C-CCGAGG is described in ClinVar as [Likely_benign]. Clinvar id is 300394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.-35_-31dupAGGCG		5_prime_UTR_variant	Exon 1 of 70	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.-35_-31dupAGGCG		5_prime_UTR_variant	Exon 1 of 70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

56853

AN:

150148

Hom.:

13447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0937

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.407

Gnomad FIN

AF:

0.544

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.379

GnomAD2 exomes

AF:

0.394

AC:

AN:

246

AF XY:

0.387

show subpopulations

Gnomad NFE exome

AF:

0.406

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.400

AC:

8999

AN:

22518

Hom.:

2201

Cov.:

AF XY:

0.391

AC XY:

5554

AN XY:

14208

show subpopulations

African (AFR)

AF:

0.117

AC:

AN:

154

American (AMR)

AF:

0.286

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

120

AN:

322

East Asian (EAS)

AF:

0.417

AC:

AN:

156

South Asian (SAS)

AF:

0.332

AC:

2101

AN:

6334

European-Finnish (FIN)

AF:

0.441

AC:

561

AN:

1272

Middle Eastern (MID)

AF:

0.240

AC:

124

AN:

516

European-Non Finnish (NFE)

AF:

0.442

AC:

5674

AN:

12828

Other (OTH)

AF:

0.364

AC:

320

AN:

880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

193

386

580

773

966

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.378

AC:

56835

AN:

150254

Hom.:

13441

Cov.:

AF XY:

0.381

AC XY:

27901

AN XY:

73326

show subpopulations

African (AFR)

AF:

0.0936

AC:

3854

AN:

41190

American (AMR)

AF:

0.378

AC:

5741

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1518

AN:

3452

East Asian (EAS)

AF:

0.515

AC:

2510

AN:

4874

South Asian (SAS)

AF:

0.406

AC:

1948

AN:

4796

European-Finnish (FIN)

AF:

0.544

AC:

5569

AN:

10238

Middle Eastern (MID)

AF:

0.286

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.511

AC:

34379

AN:

67236

Other (OTH)

AF:

0.377

AC:

789

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1516

3031

4547

6062

7578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.322

Hom.:

703

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 15, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 27, 2022

Clinical Genetics Laboratory, Skane University Hospital Lund

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside ROI, common in our data set -

CDH23-related disorder

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hearing loss, autosomal recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa-deafness syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.030

Mutation Taster

=159/41

polymorphism (auto)

(source)

Splicing

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.

NM_022124.6:c.-35_-31dupAGGCG

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