rs547034667
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM5PP3PP5
The NM_022124.6(CDH23):c.8378G>A(p.Arg2793Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2793W) has been classified as Likely pathogenic.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.8378G>A | p.Arg2793Gln | missense_variant | 59/70 | ENST00000224721.12 | |
CDH23 | NM_001171933.1 | c.1658G>A | p.Arg553Gln | missense_variant | 12/23 | ||
CDH23 | NM_001171934.1 | c.1658G>A | p.Arg553Gln | missense_variant | 12/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.8378G>A | p.Arg2793Gln | missense_variant | 59/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248702Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135008
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461642Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727100
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74478
ClinVar
Submissions by phenotype
Usher syndrome type 1D Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Dec 03, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 30, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2793 of the CDH23 protein (p.Arg2793Gln). This variant is present in population databases (rs547034667, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 522663). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at