rs41281334
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_022124.6(CDH23):c.6847G>A(p.Val2283Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0457 in 1,613,470 control chromosomes in the GnomAD database, including 2,222 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V2283L) 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.6847G>A | p.Val2283Ile | missense_variant | 50/70 | ENST00000224721.12 | |
CDH23 | NM_001171933.1 | c.127G>A | p.Val43Ile | missense_variant | 3/23 | ||
CDH23 | NM_001171934.1 | c.127G>A | p.Val43Ile | missense_variant | 3/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.6847G>A | p.Val2283Ile | missense_variant | 50/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0385 AC: 5859AN: 152140Hom.: 164 Cov.: 32
GnomAD3 exomes AF: 0.0554 AC: 13802AN: 249244Hom.: 747 AF XY: 0.0504 AC XY: 6810AN XY: 135224
GnomAD4 exome AF: 0.0465 AC: 67919AN: 1461212Hom.: 2057 Cov.: 32 AF XY: 0.0451 AC XY: 32779AN XY: 726942
GnomAD4 genome AF: 0.0385 AC: 5860AN: 152258Hom.: 165 Cov.: 32 AF XY: 0.0385 AC XY: 2864AN XY: 74452
ClinVar
Submissions by phenotype
not specified Benign:5
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 | Eurofins Ntd Llc (ga) | Jul 01, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 03, 2021 | - - |
not provided Benign:2Other:1
not provided, no classification provided | literature only | NEI Ophthalmic Genomics Laboratory, National Institutes of Health | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Usher syndrome type 1D Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Autosomal recessive nonsyndromic hearing loss 12 Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Usher syndrome type 1 Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at