rs10823849

Variant names:

• chr10-71802987-G-A
• rs10823849
• NM_022124.6:c.7572G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-71802987-G-A
• chr10-71802987-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022124.6(CDH23):​c.7572G>A​(p.Ala2524Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,613,728 control chromosomes in the GnomAD database, including 70,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6163 hom., cov: 32)
  • Exomes 𝑓: 0.29 (64362 hom.)
• Consequence: CDH23 NM_022124.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.97

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 10-71802987-G-A is Benign according to our data. Variant chr10-71802987-G-A is described in ClinVar as [Benign]. Clinvar id is 46034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71802987-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.7572G>A	p.Ala2524Ala	synonymous_variant	Exon 54 of 70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.852G>A	p.Ala284Ala	synonymous_variant	Exon 7 of 23		NP_001165404.1
CDH23	NM_001171934.1	c.852G>A	p.Ala284Ala	synonymous_variant	Exon 7 of 22		NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.7572G>A	p.Ala2524Ala	synonymous_variant	Exon 54 of 70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41987 AN: 151946 Hom.: 6157 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.261

GnomAD3 exomes AF: 0.311 AC: 77390 AN: 249164 Hom.: 13107 AF XY: 0.300 AC XY: 40505 AN XY: 135194

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.430

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.527

Gnomad SAS exome AF: 0.250

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.285

GnomAD4 exome AF: 0.290 AC: 423505 AN: 1461662 Hom.: 64362 Cov.: 45 AF XY: 0.286 AC XY: 208009 AN XY: 727116

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.276 AC: 42013 AN: 152066 Hom.: 6163 Cov.: 32 AF XY: 0.280 AC XY: 20835 AN XY: 74330

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.259

Alfa AF: 0.262 Hom.: 2774

Bravo AF: 0.278

Asia WGS AF: 0.358 AC: 1245 AN: 3478

EpiCase AF: 0.256

EpiControl AF: 0.258

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Jun 12, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 08, 2013

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. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Usher syndrome type 1D Benign:1

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. -

Usher syndrome type 1 Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 12 Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.055
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs10823849; hg19: chr10-73562744; COSMIC: COSV56453841;