rs3802719

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022124.6(CDH23):c.429+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 1,610,480 control chromosomes in the GnomAD database, including 364,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41212 hom., cov: 33)

Exomes 𝑓: 0.66 ( 323219 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Splicing: ADA: 0.00001863

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.66

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-AS1 (HGNC:31433): (CDH23 antisense RNA 1)

CDH23-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 10-71511225-G-A is Benign according to our data. Variant chr10-71511225-G-A is described in ClinVar as [Benign]. Clinvar id is 45940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71511225-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 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.429+13G>A		intron_variant		ENST00000224721.12	NP_071407.4
CDH23-AS1	NR_120672.1 linkuse as main transcript	n.143+553C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.429+13G>A		intron_variant		5	NM_022124.6	ENSP00000224721	P1	Q9H251-1
CDH23-AS1	ENST00000428918.1 linkuse as main transcript	n.96+553C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.726

AC:

110146

AN:

151694

Hom.:

41167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.905

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.734

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.634

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.696

GnomAD3 exomes

AF:

0.659

AC:

164153

AN:

249118

Hom.:

55880

AF XY:

0.658

AC XY:

88927

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.917

Gnomad AMR exome

AF:

0.456

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.597

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.663

Gnomad OTH exome

AF:

0.658

GnomAD4 exome

AF:

0.662

AC:

966220

AN:

1458666

Hom.:

323219

Cov.:

AF XY:

0.661

AC XY:

479683

AN XY:

725832

show subpopulations

Gnomad4 AFR exome

AF:

0.921

Gnomad4 AMR exome

AF:

0.466

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.758

Gnomad4 SAS exome

AF:

0.603

Gnomad4 FIN exome

AF:

0.726

Gnomad4 NFE exome

AF:

0.658

Gnomad4 OTH exome

AF:

0.681

GnomAD4 genome

AF:

0.726

AC:

110241

AN:

151814

Hom.:

41212

Cov.:

AF XY:

0.726

AC XY:

53842

AN XY:

74180

show subpopulations

Gnomad4 AFR

AF:

0.905

Gnomad4 AMR

AF:

0.575

Gnomad4 ASJ

AF:

0.734

Gnomad4 EAS

AF:

0.778

Gnomad4 SAS

AF:

0.591

Gnomad4 FIN

AF:

0.746

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.670

Hom.:

54546

Bravo

AF:

0.719

Asia WGS

AF:

0.676

AC:

2354

AN:

3478

EpiCase

AF:

0.654

EpiControl

AF:

0.653

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 02, 2012	Inferred frequency = 185/301 -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

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

Usher syndrome type 1D

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

Autosomal recessive nonsyndromic hearing loss 12

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

-0.81

CADD

Benign

0.013

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0

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

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