10-71511238-A-G

Position:

• chr10-71511238-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022124.6(CDH23):​c.429+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,601,118 control chromosomes in the GnomAD database, including 363,819 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41854 hom., cov: 33)
  • Exomes 𝑓: 0.66 (321965 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.23

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-71511238-A-G is Benign according to our data. Variant chr10-71511238-A-G is described in ClinVar as [Benign]. Clinvar id is 261548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71511238-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.429+26A>G		intron_variant		ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.429+26A>G		intron_variant		5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.731 AC: 110878 AN: 151734 Hom.: 41808 Cov.: 33

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.699

GnomAD3 exomes AF: 0.660 AC: 164324 AN: 248910 Hom.: 56077 AF XY: 0.659 AC XY: 89011 AN XY: 135058

Gnomad AFR exome AF: 0.930

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.733

Gnomad EAS exome AF: 0.778

Gnomad SAS exome AF: 0.601

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.663 AC: 961402 AN: 1449264 Hom.: 321965 Cov.: 29 AF XY: 0.662 AC XY: 477697 AN XY: 721822

Gnomad4 AFR exome AF: 0.934

Gnomad4 AMR exome AF: 0.467

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.758

Gnomad4 SAS exome AF: 0.606

Gnomad4 FIN exome AF: 0.726

Gnomad4 NFE exome AF: 0.658

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.731 AC: 110976 AN: 151854 Hom.: 41854 Cov.: 33 AF XY: 0.730 AC XY: 54194 AN XY: 74202

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.695

Alfa AF: 0.696 Hom.: 9253

Bravo AF: 0.724

Asia WGS AF: 0.681 AC: 2370 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Usher syndrome type 1D Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Autosomal recessive nonsyndromic hearing loss 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.48

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: rs3802718; hg19: chr10-73270995;