rs2394829

Positions:

• chr10-71585623-G-A
• chr10-71585623-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022124.6(CDH23):​c.832+7631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,092 control chromosomes in the GnomAD database, including 43,017 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 0.75 (43017 hom., cov: 32)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.832+7631G>A		intron_variant		ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.832+7631G>A		intron_variant		5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113962 AN: 151974 Hom.: 42988 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.750 AC: 114038 AN: 152092 Hom.: 43017 Cov.: 32 AF XY: 0.742 AC XY: 55166 AN XY: 74320

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.753

Alfa AF: 0.740 Hom.: 56667

Bravo AF: 0.752

Asia WGS AF: 0.661 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2394829; hg19: chr10-73345380;