10-71702048-G-A

Position:

chr10-71702048-G-A

Variant summary

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

The NM_022124.6(CDH23):c.2424G>A(p.Gly808=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,613,768 control chromosomes in the GnomAD database, including 1,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 221 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1759 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -1.16

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=-0.78).

BP6

Variant 10-71702048-G-A is Benign according to our data. Variant chr10-71702048-G-A is described in ClinVar as [Benign]. Clinvar id is 45897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71702048-G-A is described in Lovd as [Benign]. Variant chr10-71702048-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDH23	NM_022124.6 linkuse as main transcript	c.2424G>A	p.Gly808=	synonymous_variant	23/70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171930.2 linkuse as main transcript	c.2424G>A	p.Gly808=	synonymous_variant	23/32		NP_001165401.1
CDH23	NM_001171931.2 linkuse as main transcript	c.2424G>A	p.Gly808=	synonymous_variant	23/26		NP_001165402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.2424G>A	p.Gly808=	synonymous_variant	23/70	5	NM_022124.6	ENSP00000224721	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3106

AN:

152172

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0439

AC:

10921

AN:

248978

Hom.:

1000

AF XY:

0.0366

AC XY:

4948

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.0228

Gnomad FIN exome

AF:

0.00520

Gnomad NFE exome

AF:

0.00227

Gnomad OTH exome

AF:

0.0324

GnomAD4 exome

AF:

0.0146

AC:

21391

AN:

1461478

Hom.:

1759

Cov.:

AF XY:

0.0141

AC XY:

10265

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.0242

Gnomad4 FIN exome

AF:

0.00532

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0206

AC:

3130

AN:

152290

Hom.:

221

Cov.:

AF XY:

0.0228

AC XY:

1701

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00286

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.190

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.00687

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.00580

Hom.:

Bravo

AF:

0.0301

Asia WGS

AF:

0.0870

AC:

301

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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	GeneDx	Mar 05, 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	Eurofins Ntd Llc (ga)	Oct 08, 2013	- -

not provided

Benign:3

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	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Usher syndrome type 1D

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
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:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
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. -

Usher syndrome type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

3.9

DANN

Benign

0.46

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