NM_022124.6:c.-176_-170dupGAGCGGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_022124.6(CDH23):c.-176_-170dupGAGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 175,626 control chromosomes in the GnomAD database, including 68 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.017 ( 68 hom., cov: 30)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

CDH23
NM_022124.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 1.67

Publications

1 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 -9 ACMG points.

BP6

Variant 10-71397124-T-TGCGAGCG is Benign according to our data. Variant chr10-71397124-T-TGCGAGCG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 300390.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Benign=1}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.-176_-170dupGAGCGGC		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.-176_-170dupGAGCGGC		5_prime_UTR_variant	Exon 1 of 70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2547

AN:

147714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0573

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00795

Gnomad ASJ

AF:

0.00350

Gnomad EAS

AF:

0.000631

Gnomad SAS

AF:

0.000663

Gnomad FIN

AF:

0.0000991

Gnomad MID

AF:

0.0145

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.0141

GnomAD4 exome

AF:

0.000612

AC:

AN:

27782

Hom.:

Cov.:

AF XY:

0.000824

AC XY:

AN XY:

18196

show subpopulations

African (AFR)

AF:

0.0179

AC:

AN:

168

American (AMR)

AF:

0.0149

AC:

AN:

134

Ashkenazi Jewish (ASJ)

AF:

0.00292

AC:

AN:

342

East Asian (EAS)

AF:

0.00292

AC:

AN:

342

South Asian (SAS)

AF:

0.00

AC:

AN:

6138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000384

AC:

AN:

18242

Other (OTH)

AF:

0.00293

AC:

AN:

1024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0173

AC:

2554

AN:

147844

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1184

AN XY:

72204

show subpopulations

African (AFR)

AF:

0.0573

AC:

2301

AN:

40130

American (AMR)

AF:

0.00794

AC:

119

AN:

14980

Ashkenazi Jewish (ASJ)

AF:

0.00350

AC:

AN:

3430

East Asian (EAS)

AF:

0.000633

AC:

AN:

4742

South Asian (SAS)

AF:

0.000663

AC:

AN:

4526

European-Finnish (FIN)

AF:

0.0000991

AC:

AN:

10094

Middle Eastern (MID)

AF:

0.0154

AC:

AN:

260

European-Non Finnish (NFE)

AF:

0.00123

AC:

AN:

66726

Other (OTH)

AF:

0.0140

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

119

237

356

474

593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

CDH23-related disorder

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hearing loss, autosomal recessive

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa-deafness syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Oct 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Mutation Taster

=298/2

polymorphism

(source)

Splicing

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

Publications

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NM_022124.6:c.-176_-170dupGAGCGGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over