chr10-71803371-G-C

Variant summary

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

The NM_022124.6(CDH23):​c.7823G>C​(p.Arg2608Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

CDH23
NM_022124.6 missense

Scores

2
11
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.78
Variant links:
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]

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ACMG classification

Classification made for transcript

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
CDH23NM_022124.6 linkc.7823G>C p.Arg2608Pro missense_variant Exon 55 of 70 ENST00000224721.12 NP_071407.4 Q9H251-1Q6P152
CDH23NM_001171933.1 linkc.1103G>C p.Arg368Pro missense_variant Exon 8 of 23 NP_001165404.1 Q9H251-7
CDH23NM_001171934.1 linkc.1103G>C p.Arg368Pro missense_variant Exon 8 of 22 NP_001165405.1 Q9H251-9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH23ENST00000224721.12 linkc.7823G>C p.Arg2608Pro missense_variant Exon 55 of 70 5 NM_022124.6 ENSP00000224721.9 Q9H251-1

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
Pathogenic
0.77
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0024
T;T;.;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Benign
0.073
D
MetaRNN
Uncertain
0.59
D;D;D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
-1.1
.;N;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.59
.;.;.;N
REVEL
Uncertain
0.42
Sift
Benign
0.21
.;.;.;T
Sift4G
Uncertain
0.0060
D;.;T;T
Polyphen
1.0
.;D;.;.
Vest4
0.72
MutPred
0.70
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);.;.;
MVP
0.72
MPC
0.22
ClinPred
0.98
D
GERP RS
4.5
Varity_R
0.58
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr10-73563128; API