rs1554876347

Positions:

• chr10-71803312-G-C
• chr10-71803312-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022124.6(CDH23):​c.7764G>C​(p.Glu2588Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E2588Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDH23 NM_022124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09408069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.7764G>C	p.Glu2588Asp	missense_variant	55/70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.1044G>C	p.Glu348Asp	missense_variant	8/23		NP_001165404.1
CDH23	NM_001171934.1	c.1044G>C	p.Glu348Asp	missense_variant	8/22		NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.7764G>C	p.Glu2588Asp	missense_variant	55/70	5	NM_022124.6	ENSP00000224721	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.022	T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.62	T;T;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.094	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.95	.;L;.;.
MutationTaster	Benign	0.92	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.45	.;.;.;N
REVEL	Benign	0.071
Sift	Benign	0.52	.;.;.;T
Sift4G	Uncertain	0.0050	D;.;T;D
Polyphen		0.0	.;B;.;.
Vest4		0.14
MutPred		0.42		Loss of glycosylation at P2590 (P = 0.1179);Loss of glycosylation at P2590 (P = 0.1179);.;.;
MVP		0.49
MPC		0.13
ClinPred		0.065	T
GERP RS		4.1
Varity_R		0.052
gMVP		0.18

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: chr10-73563069;