rs7087735

Variant names:

• chr10-71567000-C-T
• rs7087735
• NM_022124.6:c.624+64C>T

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.624+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,490,842 control chromosomes in the GnomAD database, including 94,327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9779 hom., cov: 32)
  • Exomes 𝑓: 0.35 (84548 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.68
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-71567000-C-T is Benign according to our data. Variant chr10-71567000-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1177610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.624+64C>T		intron_variant	Intron 7 of 69	ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.624+64C>T		intron_variant	Intron 7 of 69	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53679 AN: 151876 Hom.: 9773 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.353 AC: 472155 AN: 1338848 Hom.: 84548 AF XY: 0.353 AC XY: 234915 AN XY: 666138

African (AFR) AF: 0.387 AC: 12076 AN: 31230

American (AMR) AF: 0.372 AC: 15427 AN: 41518

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 8559 AN: 24988

East Asian (EAS) AF: 0.544 AC: 20645 AN: 37918

South Asian (SAS) AF: 0.391 AC: 32027 AN: 81992

European-Finnish (FIN) AF: 0.309 AC: 12344 AN: 39986

Middle Eastern (MID) AF: 0.329 AC: 1806 AN: 5494

European-Non Finnish (NFE) AF: 0.342 AC: 349100 AN: 1019380

Other (OTH) AF: 0.358 AC: 20171 AN: 56342

GnomAD4 genome AF: 0.353 AC: 53707 AN: 151994 Hom.: 9779 Cov.: 32 AF XY: 0.352 AC XY: 26136 AN XY: 74290

African (AFR) AF: 0.382 AC: 15835 AN: 41448

American (AMR) AF: 0.337 AC: 5152 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1205 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2701 AN: 5164

South Asian (SAS) AF: 0.408 AC: 1961 AN: 4806

European-Finnish (FIN) AF: 0.299 AC: 3156 AN: 10556

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22766 AN: 67956

Other (OTH) AF: 0.325 AC: 688 AN: 2116

Alfa AF: 0.343 Hom.: 1880

Bravo AF: 0.357

Asia WGS AF: 0.474 AC: 1647 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 01, 2021

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 12 Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Likely 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	-0.91
CADD	Benign	0.53
DANN	Benign	0.55
PhyloP100		-1.7
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: rs7087735; hg19: chr10-73326757;