rs397517359

Positions:

• chr10-71807932-TACAGCATTCTGGCCATCC-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP3

The NM_022124.6(CDH23):​c.8650_8667delAGCATTCTGGCCATCCAC​(p.Ser2884_His2889del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDH23 NM_022124.6 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.99

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_022124.6.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.8650_8667delAGCATTCTGGCCATCCAC	p.Ser2884_His2889del	conservative_inframe_deletion	60/70	ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.1930_1947delAGCATTCTGGCCATCCAC	p.Ser644_His649del	conservative_inframe_deletion	13/23		NP_001165404.1
CDH23	NM_001171934.1	c.1930_1947delAGCATTCTGGCCATCCAC	p.Ser644_His649del	conservative_inframe_deletion	13/22		NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.8650_8667delAGCATTCTGGCCATCCAC	p.Ser2884_His2889del	conservative_inframe_deletion	60/70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Nov 15, 2011

The Ser2884_His2889del variant in CDH23 has not been reported in the literature nor previously identified by our laboratory. This variant results in an in-frame deletion of 5 amino acids located in the cadherin domain of the CDH23 protein p roduct, however its impact on the function of the protein cannot be predicted. I n summary, the clinical significance of this protein cannot be determined with c ertainty at this time. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs397517359; hg19: chr10-73567689;