Submissions for variant NM_022124.6(CDH23):c.2878G>A (p.Glu960Lys)

gnomAD frequency: 0.00299  dbSNP: rs111033458

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039137	SCV000062819	benign	not specified	2013-06-11	criteria provided, single submitter	clinical testing	The Glu960Lys variant in CDH23: 0.4% (35/8368) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs111033458).
CeGaT Center for Human Genetics Tuebingen	RCV000488332	SCV000574844	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	CDH23: BP4, BS2
GeneDx	RCV000488332	SCV000718739	benign	not provided	2018-10-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 18429043, 32707200)
Invitae	RCV000488332	SCV001096030	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000488332	SCV001143504	benign	not provided	2019-07-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001106483	SCV001263556	uncertain significance	Autosomal recessive nonsyndromic hearing loss 12	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001106484	SCV001263557	benign	Usher syndrome type 1D	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000488332	SCV002011391	benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000039137	SCV002500345	benign	not specified	2022-03-12	criteria provided, single submitter	clinical testing	Variant summary: CDH23 c.2878G>A (p.Glu960Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.003 in 245864 control chromosomes, predominantly at a frequency of 0.005 within the Non-Finnish European subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in CDH23 causing Usher Syndrome phenotype (0.0032), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. Although reported in the literature, to our knowledge, no penetrant association of c.2878G>A in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories report a majority consensus as benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV003944923	SCV004766740	likely benign	CDH23-related condition	2019-10-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc.	RCV001272548	SCV001454640	benign	Usher syndrome type 1	2020-04-15	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000039137	SCV001926187	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000488332	SCV001974791	likely benign	not provided		no assertion criteria provided	clinical testing