rs41281334

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022124.6(CDH23):c.6847G>A(p.Val2283Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0457 in 1,613,470 control chromosomes in the GnomAD database, including 2,222 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 165 hom., cov: 32)

Exomes 𝑓: 0.046 ( 2057 hom. )

Consequence

CDH23
NM_022124.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13O:1

Conservation

PhyloP100: 3.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013784468).

BP6

Variant 10-71798371-G-A is Benign according to our data. Variant chr10-71798371-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 46019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71798371-G-A is described in Lovd as [Benign]. Variant chr10-71798371-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.6847G>A	p.Val2283Ile	missense_variant	Exon 50 of 70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152
CDH23	NM_001171933.1 link	c.127G>A	p.Val43Ile	missense_variant	Exon 3 of 23		NP_001165404.1	Q9H251-7
CDH23	NM_001171934.1 link	c.127G>A	p.Val43Ile	missense_variant	Exon 3 of 22		NP_001165405.1	Q9H251-9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.6847G>A	p.Val2283Ile	missense_variant	Exon 50 of 70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5859

AN:

152140

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0937

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0554

AC:

13802

AN:

249244

Hom.:

747

AF XY:

0.0504

AC XY:

6810

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.00929

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.0486

Gnomad SAS exome

AF:

0.0273

Gnomad FIN exome

AF:

0.0366

Gnomad NFE exome

AF:

0.0412

Gnomad OTH exome

AF:

0.0562

GnomAD4 exome

AF:

0.0465

AC:

67919

AN:

1461212

Hom.:

2057

Cov.:

AF XY:

0.0451

AC XY:

32779

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.00851

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.0339

Gnomad4 SAS exome

AF:

0.0276

Gnomad4 FIN exome

AF:

0.0393

Gnomad4 NFE exome

AF:

0.0465

Gnomad4 OTH exome

AF:

0.0409

GnomAD4 genome

AF:

0.0385

AC:

5860

AN:

152258

Hom.:

165

Cov.:

AF XY:

0.0385

AC XY:

2864

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0939

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.0434

Gnomad4 SAS

AF:

0.0251

Gnomad4 FIN

AF:

0.0335

Gnomad4 NFE

AF:

0.0453

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0402

Hom.:

274

Bravo

AF:

0.0450

TwinsUK

AF:

0.0526

AC:

195

ALSPAC

AF:

0.0516

AC:

199

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.0459

AC:

391

ExAC

AF:

0.0493

AC:

5979

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

EpiCase

AF:

0.0405

EpiControl

AF:

0.0399

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jan 08, 2013

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. -

Jun 12, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 03, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3Other:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1D

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Usher syndrome type 1

Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.2

DANN

Benign

0.27

DEOGEN2

Benign

0.010

T;T;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.73

T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.49

.;.;.;N

REVEL

Benign

0.057

Sift

Benign

1.0

.;.;.;T

Sift4G

Benign

0.70

T;.;T;T

Polyphen

0.014

.;B;.;.

Vest4

0.077

MPC

0.12

ClinPred

0.0024

GERP RS

3.2

Varity_R

0.036

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over