Variant 10-71778352-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022124.6(CDH23):c.5187+44C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,608,898 control chromosomes in the GnomAD database, including 122,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13310 hom., cov: 32)

Exomes 𝑓: 0.38 ( 109167 hom. )

Consequence

CDH23
NM_022124.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.211

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 10-71778352-C-G is Benign according to our data. Variant chr10-71778352-C-G is described in ClinVar as [Benign]. Clinvar id is 261551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71778352-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6 linkuse as main transcript	c.5187+44C>G		intron_variant		ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.5187+44C>G		intron_variant		5	NM_022124.6	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62875

AN:

151882

Hom.:

13291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.359

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.383

GnomAD3 exomes

AF:

0.406

AC:

98939

AN:

243630

Hom.:

20330

AF XY:

0.396

AC XY:

52368

AN XY:

132236

show subpopulations

Gnomad AFR exome

AF:

0.496

Gnomad AMR exome

AF:

0.476

Gnomad ASJ exome

AF:

0.363

Gnomad EAS exome

AF:

0.485

Gnomad SAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.435

Gnomad NFE exome

AF:

0.373

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.384

AC:

560138

AN:

1456898

Hom.:

109167

Cov.:

AF XY:

0.382

AC XY:

276874

AN XY:

724310

show subpopulations

Gnomad4 AFR exome

AF:

0.498

Gnomad4 AMR exome

AF:

0.466

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.523

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.427

Gnomad4 NFE exome

AF:

0.374

Gnomad4 OTH exome

AF:

0.388

GnomAD4 genome

AF:

0.414

AC:

62943

AN:

152000

Hom.:

13310

Cov.:

AF XY:

0.414

AC XY:

30784

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.487

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.435

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.380

Alfa

AF:

0.308

Hom.:

1243

Bravo

AF:

0.417

Asia WGS

AF:

0.407

AC:

1416

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Usher syndrome type 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Autosomal recessive nonsyndromic hearing loss 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.1

DANN

Benign

0.74

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