chr10-71809992-C-T

Variant names:

• chr10-71809992-C-T
• rs11000009
• NM_022124.6:c.8895C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022124.6(CDH23):​c.8895C>T​(p.Pro2965Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,612,096 control chromosomes in the GnomAD database, including 11,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1003 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10793 hom.)
• Consequence: CDH23 NM_022124.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -5.42

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]

LOC124902446 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-71809992-C-T is Benign according to our data. Variant chr10-71809992-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 46058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71809992-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.8895C>T	p.Pro2965Pro	synonymous_variant	Exon 61 of 70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.2175C>T	p.Pro725Pro	synonymous_variant	Exon 14 of 23		NP_001165404.1
CDH23	NM_001171934.1	c.2175C>T	p.Pro725Pro	synonymous_variant	Exon 14 of 22		NP_001165405.1
LOC124902446	XR_007062185.1	n.1901G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.8895C>T	p.Pro2965Pro	synonymous_variant	Exon 61 of 70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16641 AN: 152108 Hom.: 1003 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0905

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.111 AC: 27274 AN: 246734 Hom.: 1794 AF XY: 0.116 AC XY: 15569 AN XY: 134096

Gnomad AFR exome AF: 0.0977

Gnomad AMR exome AF: 0.0636

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.00340

Gnomad SAS exome AF: 0.136

Gnomad FIN exome AF: 0.0962

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.116 AC: 169745 AN: 1459870 Hom.: 10793 Cov.: 33 AF XY: 0.119 AC XY: 86298 AN XY: 726194

Gnomad4 AFR exome AF: 0.0946

Gnomad4 AMR exome AF: 0.0664

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.00229

Gnomad4 SAS exome AF: 0.137

Gnomad4 FIN exome AF: 0.0942

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.109 AC: 16640 AN: 152226 Hom.: 1003 Cov.: 32 AF XY: 0.108 AC XY: 8033 AN XY: 74424

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.0903

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0944

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.120

Alfa AF: 0.124 Hom.: 536

Bravo AF: 0.106

Asia WGS AF: 0.0520 AC: 182 AN: 3478

EpiCase AF: 0.139

EpiControl AF: 0.135

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Dec 27, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 12, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1D Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 12 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1 Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.9
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs11000009; hg19: chr10-73569749;