chr10-71646691-G-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_052836.4(CDH23):c.1523G>T(p.Cys508Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,613,648 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 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. C508Y) has been classified as Likely benign.
Frequency
Consequence
NM_052836.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.1449+74G>T | intron_variant | Intron 14 of 69 | ENST00000224721.12 | NP_071407.4 | ||
CDH23 | NM_052836.4 | c.1523G>T | p.Cys508Phe | missense_variant | Exon 14 of 14 | NP_443068.1 | ||
CDH23 | NM_001171930.2 | c.1449+74G>T | intron_variant | Intron 14 of 31 | NP_001165401.1 | |||
CDH23 | NM_001171931.2 | c.1449+74G>T | intron_variant | Intron 14 of 25 | NP_001165402.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00817 AC: 1243AN: 152168Hom.: 23 Cov.: 33
GnomAD3 exomes AF: 0.00221 AC: 546AN: 247558Hom.: 13 AF XY: 0.00176 AC XY: 237AN XY: 134426
GnomAD4 exome AF: 0.000929 AC: 1357AN: 1461362Hom.: 22 Cov.: 31 AF XY: 0.000776 AC XY: 564AN XY: 726894
GnomAD4 genome AF: 0.00818 AC: 1246AN: 152286Hom.: 23 Cov.: 33 AF XY: 0.00771 AC XY: 574AN XY: 74460
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Cys508Phe in Exon 14 of CDH23: This variant is not expected to have clinical sig nificance because it has been identified in 2.7% (88/3278) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs115450602). - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2018 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
CDH23-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 24, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at