rs41281330
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_022124.6(CDH23):c.4858G>A(p.Val1620Met) variant causes a missense change. The variant allele was found at a frequency of 0.0144 in 1,611,636 control chromosomes in the GnomAD database, including 365 homozygotes. In-silico tool predicts 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. V1620G) 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.4858G>A | p.Val1620Met | missense_variant | 39/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.4858G>A | p.Val1620Met | missense_variant | 39/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0115 AC: 1744AN: 152138Hom.: 24 Cov.: 32
GnomAD3 exomes AF: 0.0174 AC: 4236AN: 243606Hom.: 89 AF XY: 0.0195 AC XY: 2582AN XY: 132466
GnomAD4 exome AF: 0.0148 AC: 21534AN: 1459380Hom.: 341 Cov.: 32 AF XY: 0.0160 AC XY: 11631AN XY: 725712
GnomAD4 genome ? AF: 0.0115 AC: 1747AN: 152256Hom.: 24 Cov.: 32 AF XY: 0.0120 AC XY: 895AN XY: 74440
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 27, 2010 | Val1620Met in exon 39 of CDH23: This variant is not expected to have clinical si gnificance due to its occurrence at a similar frequency in the general populatio n and it has been reported as presumed non-pathogenic (Astuto 2002, Oshima 2008, Ouyang 2005). In addition, this variant is listed in dbSNP (rs41281330 - no fre quency data). - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 18, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 20, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | CDH23: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 23591405, 27884173, 30245029) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 19, 2018 | - - |
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 | Oct 02, 2023 | - - |
Usher syndrome type 1D Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Autosomal recessive nonsyndromic hearing loss 12 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | 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 determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
Autosomal recessive nonsyndromic hearing loss 12;C1832845:Usher syndrome type 1D;C4539685:Pituitary adenoma 5, multiple types Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 04, 2022 | - - |
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