Variant chr10-71397276-CCGAGG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_022124.6(CDH23):c.-35_-31del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 172,870 control chromosomes in the GnomAD database, including 1,393 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1313 hom., cov: 0)

Exomes 𝑓: 0.067 ( 80 hom. )

Consequence

CDH23
NM_022124.6 5_prime_UTR

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-71397276-CCGAGG-C is Benign according to our data. Variant chr10-71397276-CCGAGG-C is described in ClinVar as [Likely_benign]. Clinvar id is 300395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71397276-CCGAGG-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 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.-35_-31del		5_prime_UTR_variant	1/70	ENST00000224721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12 linkuse as main transcript	c.-35_-31del		5_prime_UTR_variant	1/70	5	NM_022124.6	P1	Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16378

AN:

150180

Hom.:

1304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.0437

Gnomad AMR

AF:

0.0722

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.0781

Gnomad SAS

AF:

0.0968

Gnomad FIN

AF:

0.0812

Gnomad MID

AF:

0.0955

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.0528

AC:

AN:

246

Hom.:

AF XY:

0.0493

AC XY:

AN XY:

142

show subpopulations

Gnomad SAS exome

AF:

0.00

Gnomad NFE exome

AF:

0.0513

Gnomad OTH exome

AF:

0.100

GnomAD4 exome

AF:

0.0675

AC:

1524

AN:

22584

Hom.:

AF XY:

0.0692

AC XY:

986

AN XY:

14252

show subpopulations

Gnomad4 AFR exome

AF:

0.123

Gnomad4 AMR exome

AF:

0.0714

Gnomad4 ASJ exome

AF:

0.0652

Gnomad4 EAS exome

AF:

0.0833

Gnomad4 SAS exome

AF:

0.0917

Gnomad4 FIN exome

AF:

0.0754

Gnomad4 NFE exome

AF:

0.0508

Gnomad4 OTH exome

AF:

0.0602

GnomAD4 genome

AF:

0.109

AC:

16417

AN:

150286

Hom.:

1313

Cov.:

AF XY:

0.109

AC XY:

7987

AN XY:

73344

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.0720

Gnomad4 ASJ

AF:

0.0781

Gnomad4 EAS

AF:

0.0779

Gnomad4 SAS

AF:

0.0957

Gnomad4 FIN

AF:

0.0812

Gnomad4 NFE

AF:

0.0537

Gnomad4 OTH

AF:

0.106

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Outside ROI, common in our data set -
Benign, flagged submission	clinical testing	GeneDx	Nov 12, 2017	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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hearing loss, autosomal recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa-deafness syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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