rs2305209

Variant names:

Variant summary

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

The NM_052836.4(CDH23):c.1579T>C(p.Leu527Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,603,650 control chromosomes in the GnomAD database, including 21,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1623 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19426 hom. )

Consequence

CDH23
NM_052836.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0380

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=-0.93).

BP6

Variant 10-71646747-T-C is Benign according to our data. Variant chr10-71646747-T-C is described in ClinVar as [Benign]. Clinvar id is 45870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.038 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.1449+130T>C		intron_variant	Intron 14 of 69	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152
CDH23	NM_052836.4 link	c.1579T>C	p.Leu527Leu	synonymous_variant	Exon 14 of 14		NP_443068.1	Q9H251-5
CDH23	NM_001171930.2 link	c.1449+130T>C		intron_variant	Intron 14 of 31		NP_001165401.1	Q9H251A0A087WYR8Q6P152
CDH23	NM_001171931.2 link	c.1449+130T>C		intron_variant	Intron 14 of 25		NP_001165402.1	Q9H251Q8N5B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.1449+130T>C		intron_variant	Intron 14 of 69	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.142

AC:

21529

AN:

151794

Hom.:

1625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.0671

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.144

AC:

34637

AN:

241218

Hom.:

2677

AF XY:

0.149

AC XY:

19617

AN XY:

131460

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0901

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.0748

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.161

AC:

233083

AN:

1451738

Hom.:

19426

Cov.:

AF XY:

0.162

AC XY:

116634

AN XY:

720616

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.0928

Gnomad4 ASJ exome

AF:

0.183

Gnomad4 EAS exome

AF:

0.0747

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.142

AC:

21531

AN:

151912

Hom.:

1623

Cov.:

AF XY:

0.140

AC XY:

10407

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.188

Gnomad4 EAS

AF:

0.0669

Gnomad4 SAS

AF:

0.172

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.163

Hom.:

2686

Bravo

AF:

0.142

Asia WGS

AF:

0.109

AC:

378

AN:

3478

EpiCase

AF:

0.175

EpiControl

AF:

0.177

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 17, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu527Leu in exon 14A of CDH23: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, it is not located wi th the splice consensus sequence, and has been identified in 1376/8220 (16.8%) E uropean American chromosomes and 423/3790 (11.2%) African American chromosomes b y the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu; dbSNP rs2305 209). -

Jun 01, 2017

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. -

Autosomal recessive nonsyndromic hearing loss 12;C1832845:Usher syndrome type 1D;C4539685:Pituitary adenoma 5, multiple types

Benign:1

Dec 22, 2021

Fulgent Genetics, Fulgent Genetics

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.93

CADD

Benign

4.1

DANN

Benign

0.43

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