ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.429+4G>A (rs397517328)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001089681 SCV001245165 benign Nonsyndromic hearing loss and deafness 2020-01-15 reviewed by expert panel curation The filtering allele frequency of the c.429+4G>A variant in CDH23 is 1.13% for South Asian chromosomes by gnomAD v2.1.1, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). This silent variant in CDH23 is not predicted by the computational prediction analysis using MaxEntScan to impact splicing (BP7, BP4). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel (BA1, BP7, BP4).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000039175 SCV000062859 uncertain significance not specified 2014-08-08 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The 429+4G>A varian t in CDH23 has been previously reported in two Asian families with hearing loss; however, both probands were heterozygous and a variant affecting the remaining CDH23 allele was not identified (LMM unpublished data; Ganapathy 2014). This var iant has not been identified in large population studies, but there is an insuff icient number of Asian chromosomes in these studies to assess the frequency of t he variant in the Asian population. This variant is located in the 5' splice reg ion. Computational tools do not suggest an impact to splicing and this nucleotid e position is not conserved, yet, this information is not predictive enough to r ule out pathogenicity. In summary, while the clinical significance of the 429+4G >A variant is uncertain, these data suggest that is more likely to be benign.
GeneDx RCV000039175 SCV000521014 likely benign not specified 2016-05-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000941279 SCV001087162 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001103055 SCV001259768 uncertain significance Deafness, autosomal recessive 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001103056 SCV001259769 uncertain significance 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). 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.
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787808 SCV000926818 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research

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