Variant 10-71397124-TGCGAGCG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_022124.6(CDH23):c.-176_-170delGAGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000763 in 175,598 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

CDH23
NM_022124.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:3

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 Likely_benign. Variant got -1 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00069 (102/147856) while in subpopulation SAS AF= 0.00177 (8/4526). AF 95% confidence interval is 0.000879. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6 link	c.-176_-170delGAGCGGC		5_prime_UTR_variant	1/70	ENST00000224721.12	NP_071407.4	Q9H251-1Q6P152

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721 link	c.-176_-170delGAGCGGC		5_prime_UTR_variant	1/70	5	NM_022124.6	ENSP00000224721.9		Q9H251-1

Frequencies

GnomAD3 genomes

AF:

0.000684

AC:

101

AN:

147726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000334

Gnomad ASJ

AF:

0.00204

Gnomad EAS

AF:

0.000210

Gnomad SAS

AF:

0.00177

Gnomad FIN

AF:

0.000297

Gnomad MID

AF:

0.00362

Gnomad NFE

AF:

0.000495

Gnomad OTH

AF:

0.00195

GnomAD4 exome

AF:

0.00115

AC:

AN:

27742

Hom.:

AF XY:

0.00132

AC XY:

AN XY:

18160

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00294

Gnomad4 FIN exome

AF:

0.000753

Gnomad4 NFE exome

AF:

0.000658

Gnomad4 OTH exome

AF:

0.000980

GnomAD4 genome

AF:

0.000690

AC:

102

AN:

147856

Hom.:

Cov.:

AF XY:

0.000734

AC XY:

AN XY:

72206

show subpopulations

Gnomad4 AFR

AF:

0.000996

Gnomad4 AMR

AF:

0.000334

Gnomad4 ASJ

AF:

0.00204

Gnomad4 EAS

AF:

0.000211

Gnomad4 SAS

AF:

0.00177

Gnomad4 FIN

AF:

0.000297

Gnomad4 NFE

AF:

0.000495

Gnomad4 OTH

AF:

0.00193

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CDH23-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hearing loss, autosomal recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa-deafness syndrome

Uncertain:1

Uncertain significance, 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