10-71510205-G-T

Position:

• chr10-71510205-G-T

Variant summary

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

The NM_022124.6(CDH23):​c.269G>T​(p.Arg90Leu) 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: 32)
• Consequence: CDH23 NM_022124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.52

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]

CDH23-AS1 (HGNC:31433): (CDH23 antisense RNA 1)

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/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.269G>T	p.Arg90Leu	missense_variant	4/70	ENST00000224721.12	NP_071407.4
CDH23-AS1	NR_120672.1	n.144-195C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.269G>T	p.Arg90Leu	missense_variant	4/70	5	NM_022124.6	ENSP00000224721	P1
CDH23-AS1	ENST00000428918.1	n.97-195C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;T;.;.;.;.;T;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.95	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.72	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.0	.;.;L;L;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	N;.;N;.;N;.;.;.;.
REVEL	Uncertain	0.45
Sift	Benign	0.062	T;.;T;.;T;.;.;.;.
Sift4G	Uncertain	0.018	D;D;D;T;T;.;T;D;.
Polyphen		1.0, 1.0	.;.;D;D;.;.;.;.;.
Vest4		0.89
MutPred		0.60		Loss of disorder (P = 0.0789);Loss of disorder (P = 0.0789);Loss of disorder (P = 0.0789);Loss of disorder (P = 0.0789);Loss of disorder (P = 0.0789);.;.;Loss of disorder (P = 0.0789);Loss of disorder (P = 0.0789);
MVP		0.76
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.42
gMVP		0.54

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: rs397517317; hg19: chr10-73269962;