rs4747194
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_022124.6(CDH23):c.7073G>A(p.Arg2358Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,613,004 control chromosomes in the GnomAD database, including 71,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2358W) has been classified as Uncertain significance.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.7073G>A | p.Arg2358Gln | missense_variant | 51/70 | ENST00000224721.12 | |
CDH23 | NM_001171933.1 | c.353G>A | p.Arg118Gln | missense_variant | 4/23 | ||
CDH23 | NM_001171934.1 | c.353G>A | p.Arg118Gln | missense_variant | 4/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.7073G>A | p.Arg2358Gln | missense_variant | 51/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.288 AC: 43751AN: 151980Hom.: 6581 Cov.: 33
GnomAD3 exomes AF: 0.315 AC: 78310AN: 248704Hom.: 13346 AF XY: 0.304 AC XY: 40964AN XY: 134910
GnomAD4 exome AF: 0.292 AC: 426043AN: 1460906Hom.: 65112 Cov.: 36 AF XY: 0.288 AC XY: 209353AN XY: 726744
GnomAD4 genome ? AF: 0.288 AC: 43770AN: 152098Hom.: 6585 Cov.: 33 AF XY: 0.292 AC XY: 21672AN XY: 74332
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 27, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 12, 2009 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2013 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Usher syndrome type 1D Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Autosomal recessive nonsyndromic hearing loss 12 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Usher syndrome type 1 Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at