10-71810004-C-T

Position:

chr10-71810004-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_022124.6(CDH23):c.8907C>T(p.Arg2969Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0086 in 1,612,394 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 31 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 373 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.59

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:

CDH23 (HGNC:):

CDH23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-71810004-C-T is Benign according to our data. Variant chr10-71810004-C-T is described in ClinVar as [Benign]. Clinvar id is 46059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71810004-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0828 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.8907C>T	p.Arg2969Arg	synonymous_variant	61/70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152
CDH23	NM_001171933.1 linkuse as main transcript	c.2187C>T	p.Arg729Arg	synonymous_variant	14/23		NP_001165404.1	Q9H251-7
CDH23	NM_001171934.1 linkuse as main transcript	c.2187C>T	p.Arg729Arg	synonymous_variant	14/22		NP_001165405.1	Q9H251-9
LOC124902446	XR_007062185.1 linkuse as main transcript	n.1889G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.8907C>T	p.Arg2969Arg	synonymous_variant	61/70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.00856

AC:

1303

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0229

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0897

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00896

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00373

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.0165

AC:

4065

AN:

246856

Hom.:

117

AF XY:

0.0141

AC XY:

1889

AN XY:

134162

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.0512

Gnomad ASJ exome

AF:

0.000798

Gnomad EAS exome

AF:

0.0816

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.00783

Gnomad NFE exome

AF:

0.00427

Gnomad OTH exome

AF:

0.0133

GnomAD4 exome

AF:

0.00860

AC:

12562

AN:

1460114

Hom.:

373

Cov.:

AF XY:

0.00824

AC XY:

5983

AN XY:

726280

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.0486

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.00253

Gnomad4 FIN exome

AF:

0.00696

Gnomad4 NFE exome

AF:

0.00415

Gnomad4 OTH exome

AF:

0.00951

GnomAD4 genome

AF:

0.00852

AC:

1298

AN:

152280

Hom.:

Cov.:

AF XY:

0.00959

AC XY:

714

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.0228

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0895

Gnomad4 SAS

AF:

0.00415

Gnomad4 FIN

AF:

0.00896

Gnomad4 NFE

AF:

0.00373

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00439

Hom.:

Bravo

AF:

0.0104

Asia WGS

AF:

0.0340

AC:

117

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 26, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 12, 2009	- -

Usher syndrome type 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Usher syndrome type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.7

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: -6

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