10-71511238-A-G

Variant names:

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+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,601,118 control chromosomes in the GnomAD database, including 363,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41854 hom., cov: 33)

Exomes 𝑓: 0.66 ( 321965 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.23

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=-0.9).

BP6

Variant 10-71511238-A-G is Benign according to our data. Variant chr10-71511238-A-G is described in ClinVar as [Benign]. Clinvar id is 261548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71511238-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.429+26A>G		intron_variant	Intron 6 of 69	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12 link	c.429+26A>G		intron_variant	Intron 6 of 69	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.731

AC:

110878

AN:

151734

Hom.:

41808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.492

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.734

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.699

GnomAD3 exomes

AF:

0.660

AC:

164324

AN:

248910

Hom.:

56077

AF XY:

0.659

AC XY:

89011

AN XY:

135058

show subpopulations

Gnomad AFR exome

AF:

0.930

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.733

Gnomad EAS exome

AF:

0.778

Gnomad SAS exome

AF:

0.601

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.662

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.663

AC:

961402

AN:

1449264

Hom.:

321965

Cov.:

AF XY:

0.662

AC XY:

477697

AN XY:

721822

show subpopulations

Gnomad4 AFR exome

AF:

0.934

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.758

Gnomad4 SAS exome

AF:

0.606

Gnomad4 FIN exome

AF:

0.726

Gnomad4 NFE exome

AF:

0.658

Gnomad4 OTH exome

AF:

0.683

GnomAD4 genome

AF:

0.731

AC:

110976

AN:

151854

Hom.:

41854

Cov.:

AF XY:

0.730

AC XY:

54194

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.920

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.734

Gnomad4 EAS

AF:

0.777

Gnomad4 SAS

AF:

0.597

Gnomad4 FIN

AF:

0.746

Gnomad4 NFE

AF:

0.658

Gnomad4 OTH

AF:

0.695

Alfa

AF:

0.696

Hom.:

9253

Bravo

AF:

0.724

Asia WGS

AF:

0.681

AC:

2370

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 13, 2018

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1D

Benign:1

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:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.41

DANN

Benign

0.48

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

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