chr10-71509957-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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-AS1 (HGNC:31433): (CDH23 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	NM_022124.6	MANE Select	c.146-125T>C		intron	N/A	NP_071407.4
	CDH23	NM_001171930.2		c.146-125T>C		intron	N/A	NP_001165401.1	A0A087WYR8
	CDH23	NM_001171931.2		c.146-125T>C		intron	N/A	NP_001165402.1	Q8N5B3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH23	ENST00000224721.12	TSL:5 MANE Select	c.146-125T>C		intron	N/A	ENSP00000224721.9	Q9H251-1
	CDH23	ENST00000616684.4	TSL:5	c.146-125T>C		intron	N/A	ENSP00000482036.2	A0A087WYR8
	CDH23	ENST00000398809.9	TSL:5	c.146-125T>C		intron	N/A	ENSP00000381789.5	A0A0A0MS94

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

African (AFR) AF: 0.935 AC: 21449 AN: 22950

American (AMR) AF: 0.472 AC: 17882 AN: 37862

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 14627 AN: 20102

East Asian (EAS) AF: 0.756 AC: 27264 AN: 36070

South Asian (SAS) AF: 0.606 AC: 39935 AN: 65932

European-Finnish (FIN) AF: 0.723 AC: 30206 AN: 41776

Middle Eastern (MID) AF: 0.702 AC: 3213 AN: 4574

European-Non Finnish (NFE) AF: 0.660 AC: 413104 AN: 626350

Other (OTH) AF: 0.686 AC: 28517 AN: 41584

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

African (AFR) AF: 0.925 AC: 38417 AN: 41512

American (AMR) AF: 0.578 AC: 8834 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2548 AN: 3468

East Asian (EAS) AF: 0.777 AC: 4009 AN: 5160

South Asian (SAS) AF: 0.597 AC: 2874 AN: 4816

European-Finnish (FIN) AF: 0.748 AC: 7908 AN: 10578

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44732 AN: 67962

Other (OTH) AF: 0.694 AC: 1468 AN: 2114

Alfa AF: 0.708 Hom.: 4826

Bravo AF: 0.726

Asia WGS AF: 0.682 AC: 2372 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 12 (1)
-	-	1	Pituitary adenoma 5, multiple types (1)
-	-	1	Usher syndrome type 1D (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.013
DANN	Benign	0.32
PhyloP100		-5.1
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: rs2297953; hg19: chr10-73269714;