10-71566822-C-T

Position:

chr10-71566822-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_022124.6(CDH23):c.510C>T(p.Ser170Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,613,992 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 34 hom. )

Consequence

CDH23
NM_022124.6 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:9

Conservation

PhyloP100: 1.39

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 10-71566822-C-T is Benign according to our data. Variant chr10-71566822-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 45966.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=5}. Variant chr10-71566822-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00137 (209/152336) while in subpopulation EAS AF= 0.0274 (142/5178). AF 95% confidence interval is 0.0238. There are 1 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 34 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6 linkuse as main transcript	c.510C>T	p.Ser170Ser	synonymous_variant	7/70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.510C>T	p.Ser170Ser	synonymous_variant	7/70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.00137

AC:

209

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0276

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00280

AC:

698

AN:

249030

Hom.:

AF XY:

0.00276

AC XY:

373

AN XY:

135124

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0264

Gnomad SAS exome

AF:

0.000523

Gnomad FIN exome

AF:

0.00246

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00151

AC:

2212

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1061

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0395

Gnomad4 SAS exome

AF:

0.000649

Gnomad4 FIN exome

AF:

0.00225

Gnomad4 NFE exome

AF:

0.000181

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00137

AC:

209

AN:

152336

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0274

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000303

Hom.:

Bravo

AF:

0.00156

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:9

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Feb 28, 2022	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 23, 2012	Ser170Ser in exon 7 of CDH23: This variant has been observed in patients (Nakani shi 2010, Oshima 2008, Wagatsuma 2007) but is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located near a splice junction and has been identified in 1% (21/2100) individuals (dbSNP rs143 341423). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Usher syndrome type 1D

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	May 18, 2021	- -
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. -

Autosomal recessive nonsyndromic hearing loss 12

Uncertain:1

Uncertain significance, 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

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

-0.34

CADD

Benign

DANN

Benign

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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