10-71803066-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_022124.6(CDH23):c.7651C>G(p.Pro2551Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.7651C>G | p.Pro2551Ala | missense_variant | Exon 54 of 70 | ENST00000224721.12 | NP_071407.4 | |
CDH23 | NM_001171933.1 | c.931C>G | p.Pro311Ala | missense_variant | Exon 7 of 23 | NP_001165404.1 | ||
CDH23 | NM_001171934.1 | c.931C>G | p.Pro311Ala | missense_variant | Exon 7 of 22 | NP_001165405.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248234Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134612
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457476Hom.: 0 Cov.: 38 AF XY: 0.00000276 AC XY: 2AN XY: 724140
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
The Pro2551Ala variant in CDH23 has not been previously reported in individuals with hearing loss and was absent from large population studies. Computational pr ediction tools and conservation analyses suggest that the Pro2551Ala variant may impact the protein, though this information is not predictive enough to determi ne pathogenicity. In summary, the clinical significance of the Pro2551Ala varian t is uncertain. -
Usher syndrome type 1 Uncertain:1
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not provided Uncertain:1
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at