NM_022124.6:c.8404A>C

Variant names:

• chr10-71807611-A-C
• NM_022124.6:c.8404A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022124.6(CDH23):​c.8404A>C​(p.Ile2802Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDH23 NM_022124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.19

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3827556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.8404A>C	p.Ile2802Leu	missense_variant	Exon 59 of 70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.1684A>C	p.Ile562Leu	missense_variant	Exon 12 of 23		NP_001165404.1
CDH23	NM_001171934.1	c.1684A>C	p.Ile562Leu	missense_variant	Exon 12 of 22		NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.8404A>C	p.Ile2802Leu	missense_variant	Exon 59 of 70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0086	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0065	T;T;.;.
Eigen	Benign	0.053
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	.;N;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.56	.;.;.;N
REVEL	Benign	0.19
Sift	Benign	0.33	.;.;.;T
Sift4G	Pathogenic	0.0	D;.;D;D
Polyphen		0.21	.;B;.;.
Vest4		0.36
MutPred		0.42		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;.;
MVP		0.70
MPC		0.16
ClinPred		0.88	D
GERP RS		5.6
Varity_R		0.52
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr10-73567368;