rs538435711

Variant names:

• chr10-71803233-C-G
• NM_022124.6:c.7685C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-71803233-C-G
• chr10-71803233-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022124.6(CDH23):​c.7685C>G​(p.Ser2562Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CDH23 NM_022124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.7685C>G	p.Ser2562Trp	missense_variant	Exon 55 of 70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.965C>G	p.Ser322Trp	missense_variant	Exon 8 of 23		NP_001165404.1
CDH23	NM_001171934.1	c.965C>G	p.Ser322Trp	missense_variant	Exon 8 of 22		NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.7685C>G	p.Ser2562Trp	missense_variant	Exon 55 of 70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450868 Hom.: 0 Cov.: 34 AF XY: 0.00000139 AC XY: 1 AN XY: 720772

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;D;.;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.1	.;M;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.8	.;.;.;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	.;.;.;D
Sift4G	Pathogenic	0.0010	D;.;D;D
Polyphen		0.99	.;D;.;.
Vest4		0.76
MutPred		0.44		Loss of glycosylation at S2562 (P = 0.0167);Loss of glycosylation at S2562 (P = 0.0167);.;.;
MVP		0.89
MPC		0.43
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.94
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-73562990;