chr10-71778221-C-T

Position:

chr10-71778221-C-T

Variant summary

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

The NM_022124.6(CDH23):c.5100C>T(p.Tyr1700=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,613,522 control chromosomes in the GnomAD database, including 33,605 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 2975 hom., cov: 31)

Exomes 𝑓: 0.20 ( 30630 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.91

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=-0.48).

BP6

Variant 10-71778221-C-T is Benign according to our data. Variant chr10-71778221-C-T is described in ClinVar as [Benign]. Clinvar id is 45965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71778221-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6 linkuse as main transcript	c.5100C>T	p.Tyr1700=	synonymous_variant	40/70	ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.5100C>T	p.Tyr1700=	synonymous_variant	40/70	5	NM_022124.6	ENSP00000224721	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29786

AN:

151806

Hom.:

2972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.188

GnomAD3 exomes

AF:

0.187

AC:

46533

AN:

249136

Hom.:

4556

AF XY:

0.185

AC XY:

25020

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.142

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.202

AC:

295842

AN:

1461598

Hom.:

30630

Cov.:

AF XY:

0.200

AC XY:

145667

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.126

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.220

Gnomad4 SAS exome

AF:

0.142

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.196

AC:

29796

AN:

151924

Hom.:

2975

Cov.:

AF XY:

0.196

AC XY:

14558

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.189

Gnomad4 AMR

AF:

0.158

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.204

Hom.:

1739

Bravo

AF:

0.188

Asia WGS

AF:

0.156

AC:

541

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 08, 2014	- -
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	Jan 07, 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. -

Usher syndrome type 1D

Benign:2

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

not provided

Benign:2

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

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

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

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

-0.48

CADD

Benign

0.95

DANN

Benign

0.82

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