10-71739804-C-G

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.4488+32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 1,582,254 control chromosomes in the GnomAD database, including 244,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 20464 hom., cov: 33)

Exomes 𝑓: 0.56 ( 224380 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.610

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=-0.91).

BP6

Variant 10-71739804-C-G is Benign according to our data. Variant chr10-71739804-C-G is described in ClinVar as [Benign]. Clinvar id is 261549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.4488+32C>G		intron_variant	Intron 36 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.4488+32C>G		intron_variant	Intron 36 of 69	5	NM_022124.6	ENSP00000224721.9		Q9H251-1
CDH23	ENST00000398792.3 link	n.1177+32C>G		intron_variant	Intron 7 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.511

AC:

77684

AN:

151968

Hom.:

20466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.415

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.595

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.458

Gnomad FIN

AF:

0.562

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.591

Gnomad OTH

AF:

0.537

GnomAD2 exomes

AF:

0.501

AC:

116078

AN:

231556

AF XY:

0.509

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.305

Gnomad FIN exome

AF:

0.565

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.530

GnomAD4 exome

AF:

0.555

AC:

793870

AN:

1430168

Hom.:

224380

Cov.:

AF XY:

0.554

AC XY:

392103

AN XY:

708262

show subpopulations

African (AFR)

AF:

0.405

AC:

13360

AN:

32958

American (AMR)

AF:

0.361

AC:

15655

AN:

43372

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

15092

AN:

25288

East Asian (EAS)

AF:

0.271

AC:

10619

AN:

39192

South Asian (SAS)

AF:

0.455

AC:

38273

AN:

84156

European-Finnish (FIN)

AF:

0.564

AC:

25492

AN:

45172

Middle Eastern (MID)

AF:

0.536

AC:

3047

AN:

5684

European-Non Finnish (NFE)

AF:

0.585

AC:

640444

AN:

1095154

Other (OTH)

AF:

0.539

AC:

31888

AN:

59192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

15976

31952

47927

63903

79879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.511

AC:

77693

AN:

152086

Hom.:

20464

Cov.:

AF XY:

0.508

AC XY:

37738

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.414

AC:

17184

AN:

41466

American (AMR)

AF:

0.451

AC:

6896

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.595

AC:

2065

AN:

3468

East Asian (EAS)

AF:

0.287

AC:

1484

AN:

5170

South Asian (SAS)

AF:

0.460

AC:

2220

AN:

4826

European-Finnish (FIN)

AF:

0.562

AC:

5948

AN:

10582

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.591

AC:

40145

AN:

67984

Other (OTH)

AF:

0.533

AC:

1126

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1938

3875

5813

7750

9688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.510

Hom.:

2858

Bravo

AF:

0.498

Asia WGS

AF:

0.344

AC:

1198

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

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 13, 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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.91

CADD

Benign

0.50

(source)

DANN

Benign

0.47

PhyloP100

-0.61

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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10-71739804-C-G

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