rs2297953

Variant names:

• chr10-71509957-T-C
• rs2297953
• NM_022124.6:c.146-125T>C

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.146-125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 1,049,302 control chromosomes in the GnomAD database, including 242,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (42171 hom., cov: 31)
  • Exomes 𝑓: 0.66 (200565 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -5.12

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:31433): (CDH23 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-71509957-T-C is Benign according to our data. Variant chr10-71509957-T-C is described in ClinVar as [Benign]. Clinvar id is 678765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.146-125T>C		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.146-125T>C		intron_variant	Intron 3 of 69	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111327 AN: 151984 Hom.: 42123 Cov.: 31

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.697

GnomAD4 exome AF: 0.665 AC: 596197 AN: 897200 Hom.: 200565 Cov.: 12 AF XY: 0.662 AC XY: 304995 AN XY: 460724

Gnomad4 AFR exome AF: 0.935

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.606

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.660

Gnomad4 OTH exome AF: 0.686

GnomAD4 genome AF: 0.733 AC: 111427 AN: 152102 Hom.: 42171 Cov.: 31 AF XY: 0.732 AC XY: 54417 AN XY: 74332

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.748

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.694

Alfa AF: 0.708 Hom.: 4826

Bravo AF: 0.726

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Pituitary adenoma 5, multiple types Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1D Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 12 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.013
DANN	Benign	0.32

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: rs2297953; hg19: chr10-73269714;