rs10823849

Positions:

Variant summary

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

The NM_022124.6(CDH23):c.7572G>A(p.Ala2524=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,613,728 control chromosomes in the GnomAD database, including 70,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6163 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64362 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.97

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=-0.73).

BP6

Variant 10-71802987-G-A is Benign according to our data. Variant chr10-71802987-G-A is described in ClinVar as [Benign]. Clinvar id is 46034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71802987-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH23	NM_022124.6 linkuse as main transcript	c.7572G>A	p.Ala2524=	synonymous_variant	54/70	ENST00000224721.12
CDH23	NM_001171933.1 linkuse as main transcript	c.852G>A	p.Ala284=	synonymous_variant	7/23
CDH23	NM_001171934.1 linkuse as main transcript	c.852G>A	p.Ala284=	synonymous_variant	7/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.7572G>A	p.Ala2524=	synonymous_variant	54/70	5	NM_022124.6	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41987

AN:

151946

Hom.:

6157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.311

AC:

77390

AN:

249164

Hom.:

13107

AF XY:

0.300

AC XY:

40505

AN XY:

135194

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.527

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.290

AC:

423505

AN:

1461662

Hom.:

64362

Cov.:

AF XY:

0.286

AC XY:

208009

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.226

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.575

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.279

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.276

AC:

42013

AN:

152066

Hom.:

6163

Cov.:

AF XY:

0.280

AC XY:

20835

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.330

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.531

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.262

Hom.:

2774

Bravo

AF:

0.278

Asia WGS

AF:

0.358

AC:

1245

AN:

3478

EpiCase

AF:

0.256

EpiControl

AF:

0.258

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 12, 2009	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Usher syndrome type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Usher syndrome type 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.055

DANN

Benign

0.57

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