rs192266658

Positions:

chr10-71811516-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_022124.6(CDH23):c.9204G>A(p.Ala3068=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 1,613,926 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 3 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0520

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:

LOC124902446 (HGNC:):

LOC124902446 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 10-71811516-G-A is Benign according to our data. Variant chr10-71811516-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 162952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71811516-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.052 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00261 (398/152238) while in subpopulation AFR AF= 0.00908 (377/41534). AF 95% confidence interval is 0.00832. There are 2 homozygotes in gnomad4. There are 198 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDH23	NM_022124.6 linkuse as main transcript	c.9204G>A	p.Ala3068=	synonymous_variant	64/70	ENST00000224721.12	NP_071407.4
LOC124902446	XR_007062185.1 linkuse as main transcript	n.1243C>T		non_coding_transcript_exon_variant	1/2
CDH23	NM_001171933.1 linkuse as main transcript	c.2484G>A	p.Ala828=	synonymous_variant	17/23		NP_001165404.1
CDH23	NM_001171934.1 linkuse as main transcript	c.2484G>A	p.Ala828=	synonymous_variant	17/22		NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.9204G>A	p.Ala3068=	synonymous_variant	64/70	5	NM_022124.6	ENSP00000224721	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

399

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00913

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000638

AC:

159

AN:

249140

Hom.:

AF XY:

0.000518

AC XY:

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.00904

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000289

AC:

422

AN:

1461688

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

190

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00261

AC:

398

AN:

152238

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

198

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00908

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00284

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Apr 30, 2012

Ala3068Ala in Exon 64 of CDH23: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.7% (24/3642) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). -

Usher syndrome type 1

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Natera, Inc.

Dec 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.7

DANN

Benign

0.87

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

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