rs11594082

Variant names:

• chr10-71539496-G-T
• rs11594082
• NM_022124.6:c.430-27246G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022124.6(CDH23):​c.430-27246G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 151,638 control chromosomes in the GnomAD database, including 895 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (895 hom., cov: 31)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.502
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 12

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 1D

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.430-27246G>T		intron_variant	Intron 6 of 69	ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.430-27246G>T		intron_variant	Intron 6 of 69	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15580 AN: 151520 Hom.: 890 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.000778

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.0757

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.103 AC: 15610 AN: 151638 Hom.: 895 Cov.: 31 AF XY: 0.0996 AC XY: 7381 AN XY: 74078

African (AFR) AF: 0.122 AC: 5033 AN: 41292

American (AMR) AF: 0.0813 AC: 1239 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3468

East Asian (EAS) AF: 0.000780 AC: 4 AN: 5128

South Asian (SAS) AF: 0.0373 AC: 179 AN: 4800

European-Finnish (FIN) AF: 0.0757 AC: 795 AN: 10502

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7619 AN: 67900

Other (OTH) AF: 0.106 AC: 222 AN: 2104

Alfa AF: 0.111 Hom.: 322

Bravo AF: 0.104

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11594082; hg19: chr10-73299253;