10-71541584-A-G

Variant names:

• chr10-71541584-A-G
• rs2394807
• NM_022124.6:c.430-25158A>G

Variant summary

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

The NM_022124.6(CDH23):​c.430-25158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,222 control chromosomes in the GnomAD database, including 41,113 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 0.73 (41113 hom., cov: 33)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022124.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	NM_022124.6	MANE Select	c.430-25158A>G		intron	N/A	NP_071407.4
	CDH23	NM_001171930.2		c.430-25158A>G		intron	N/A	NP_001165401.1
	CDH23	NM_001171931.2		c.430-25158A>G		intron	N/A	NP_001165402.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.430-25158A>G		intron	N/A	ENSP00000224721.9
	CDH23	ENST00000616684.4	TSL:5	c.430-25158A>G		intron	N/A	ENSP00000482036.2
	CDH23	ENST00000398809.9	TSL:5	c.430-25158A>G		intron	N/A	ENSP00000381789.5

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110806 AN: 152104 Hom.: 41063 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.727

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

GnomAD4 genome AF: 0.729 AC: 110910 AN: 152222 Hom.: 41113 Cov.: 33 AF XY: 0.731 AC XY: 54366 AN XY: 74390

African (AFR) AF: 0.859 AC: 35695 AN: 41540

American (AMR) AF: 0.635 AC: 9713 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3470

East Asian (EAS) AF: 0.886 AC: 4589 AN: 5180

South Asian (SAS) AF: 0.727 AC: 3509 AN: 4828

European-Finnish (FIN) AF: 0.746 AC: 7897 AN: 10586

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44770 AN: 68012

Other (OTH) AF: 0.726 AC: 1533 AN: 2112

Alfa AF: 0.687 Hom.: 27587

Bravo AF: 0.726

Asia WGS AF: 0.800 AC: 2781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.27
PhyloP100		-2.8
Mutation Taster		=98/2	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: rs2394807; hg19: chr10-73301341;