10-71480847-C-T

Variant names:

• chr10-71480847-C-T
• rs2394800
• NM_022124.6:c.146-29235C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022124.6(CDH23):​c.146-29235C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,736 control chromosomes in the GnomAD database, including 1,833 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 0.15 (1833 hom., cov: 31)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.146-29235C>T		intron_variant	Intron 3 of 69	ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.146-29235C>T		intron_variant	Intron 3 of 69	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22955 AN: 151618 Hom.: 1835 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.151 AC: 22959 AN: 151736 Hom.: 1833 Cov.: 31 AF XY: 0.149 AC XY: 11046 AN XY: 74124

African (AFR) AF: 0.124 AC: 5123 AN: 41382

American (AMR) AF: 0.142 AC: 2160 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 329 AN: 3460

East Asian (EAS) AF: 0.221 AC: 1134 AN: 5130

South Asian (SAS) AF: 0.119 AC: 569 AN: 4800

European-Finnish (FIN) AF: 0.161 AC: 1688 AN: 10510

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11551 AN: 67920

Other (OTH) AF: 0.130 AC: 274 AN: 2110

Alfa AF: 0.150 Hom.: 3003

Bravo AF: 0.145

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.52
PhyloP100		0.29
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: rs2394800; hg19: chr10-73240604;