10-71706971-C-A
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_022124.6(CDH23):c.3028C>A(p.Arg1010Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1010C) has been classified as Uncertain significance.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal recessive nonsyndromic hearing loss 12Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
- nonsyndromic genetic hearing lossInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Usher syndrome type 1Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- Usher syndrome type 1DInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.3028C>A | p.Arg1010Ser | missense_variant | Exon 26 of 70 | ENST00000224721.12 | NP_071407.4 | |
CDH23 | NM_001171930.2 | c.3028C>A | p.Arg1010Ser | missense_variant | Exon 26 of 32 | NP_001165401.1 | ||
CDH23 | NM_001171931.2 | c.3028C>A | p.Arg1010Ser | missense_variant | Exon 26 of 26 | NP_001165402.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The Arg1010Ser variant in CDH23 has not been previously reported in individuals with hearing loss or from large population studies. Computational prediction too ls and conservation analyses suggest this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summa ry, additional information is needed to fully assess the clinical significance o f this variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at