NM_022124.6:c.2388T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022124.6(CDH23):c.2388T>C(p.Asp796Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,609,042 control chromosomes in the GnomAD database, including 374,173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30274 hom., cov: 34)

Exomes 𝑓: 0.68 ( 343899 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.296

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 10-71695516-T-C is Benign according to our data. Variant chr10-71695516-T-C is described in ClinVar as [Benign]. Clinvar id is 45896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71695516-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.296 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.2388T>C	p.Asp796Asp	synonymous_variant	Exon 22 of 70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152
CDH23	NM_001171930.2 link	c.2388T>C	p.Asp796Asp	synonymous_variant	Exon 22 of 32		NP_001165401.1	Q9H251A0A087WYR8Q6P152
CDH23	NM_001171931.2 link	c.2388T>C	p.Asp796Asp	synonymous_variant	Exon 22 of 26		NP_001165402.1	Q9H251Q8N5B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.2388T>C	p.Asp796Asp	synonymous_variant	Exon 22 of 70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

95003

AN:

152022

Hom.:

30266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.527

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.781

Gnomad EAS

AF:

0.476

Gnomad SAS

AF:

0.618

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.680

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.655

GnomAD3 exomes

AF:

0.628

AC:

156326

AN:

248862

Hom.:

50537

AF XY:

0.641

AC XY:

86511

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.521

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.764

Gnomad EAS exome

AF:

0.501

Gnomad SAS exome

AF:

0.631

Gnomad FIN exome

AF:

0.558

Gnomad NFE exome

AF:

0.711

Gnomad OTH exome

AF:

0.656

GnomAD4 exome

AF:

0.683

AC:

994764

AN:

1456902

Hom.:

343899

Cov.:

AF XY:

0.684

AC XY:

495621

AN XY:

725024

show subpopulations

Gnomad4 AFR exome

AF:

0.511

Gnomad4 AMR exome

AF:

0.475

Gnomad4 ASJ exome

AF:

0.771

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.634

Gnomad4 FIN exome

AF:

0.565

Gnomad4 NFE exome

AF:

0.712

Gnomad4 OTH exome

AF:

0.670

GnomAD4 genome

AF:

0.625

AC:

95042

AN:

152140

Hom.:

30274

Cov.:

AF XY:

0.617

AC XY:

45899

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.528

Gnomad4 AMR

AF:

0.563

Gnomad4 ASJ

AF:

0.781

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.618

Gnomad4 FIN

AF:

0.553

Gnomad4 NFE

AF:

0.711

Gnomad4 OTH

AF:

0.651

Alfa

AF:

0.694

Hom.:

45790

Bravo

AF:

0.622

Asia WGS

AF:

0.522

AC:

1818

AN:

3478

EpiCase

AF:

0.727

EpiControl

AF:

0.731

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 02, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Inferred frequency = 135/301 -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1D

Benign:2

Jan 12, 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. -

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:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jul 01, 2021

Genome-Nilou Lab

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

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.036

DANN

Benign

0.39

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

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