10-71690449-C-G

Position:

• chr10-71690449-C-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.2060-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0249 in 1,565,888 control chromosomes in the GnomAD database, including 2,565 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (288 hom., cov: 33)
  • Exomes 𝑓: 0.024 (2277 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.473

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-71690449-C-G is Benign according to our data. Variant chr10-71690449-C-G is described in ClinVar as [Benign]. Clinvar id is 136700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.2060-19C>G		intron_variant		ENST00000224721.12	NP_071407.4
CDH23	NM_001171930.2	c.2060-19C>G		intron_variant			NP_001165401.1
CDH23	NM_001171931.2	c.2060-19C>G		intron_variant			NP_001165402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.2060-19C>G		intron_variant		5	NM_022124.6	ENSP00000224721	P1

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 5063 AN: 152192 Hom.: 279 Cov.: 33

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0110

Gnomad OTH AF: 0.0354

GnomAD3 exomes AF: 0.0596 AC: 11549 AN: 193688 Hom.: 1092 AF XY: 0.0535 AC XY: 5561 AN XY: 103930

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.186

Gnomad ASJ exome AF: 0.0168

Gnomad EAS exome AF: 0.255

Gnomad SAS exome AF: 0.0372

Gnomad FIN exome AF: 0.00939

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.0513

GnomAD4 exome AF: 0.0240 AC: 33938 AN: 1413578 Hom.: 2277 Cov.: 28 AF XY: 0.0240 AC XY: 16768 AN XY: 700008

Gnomad4 AFR exome AF: 0.0179

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.0394

Gnomad4 FIN exome AF: 0.00955

Gnomad4 NFE exome AF: 0.00943

Gnomad4 OTH exome AF: 0.0328

GnomAD4 genome AF: 0.0335 AC: 5102 AN: 152310 Hom.: 288 Cov.: 33 AF XY: 0.0360 AC XY: 2679 AN XY: 74472

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.0335

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.0110

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.00951 Hom.: 4

Bravo AF: 0.0441

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 05, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	-0.82
CADD	Benign	0.50
DANN	Benign	0.60

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: rs2290024; hg19: chr10-73450206; COSMIC: COSV54951656;