rs374955091
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_022124.6(CDH23):c.2171G>A(p.Arg724His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,588,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R724G) has been classified as Uncertain significance.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.2171G>A | p.Arg724His | missense_variant | 20/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.2171G>A | p.Arg724His | missense_variant | 20/32 | ||
CDH23 | NM_001171931.2 | c.2171G>A | p.Arg724His | missense_variant | 20/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.2171G>A | p.Arg724His | missense_variant | 20/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152054Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000296 AC: 62AN: 209410Hom.: 0 AF XY: 0.000382 AC XY: 43AN XY: 112632
GnomAD4 exome AF: 0.000160 AC: 230AN: 1435872Hom.: 0 Cov.: 29 AF XY: 0.000216 AC XY: 154AN XY: 712048
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74394
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 09, 2014 | The Arg724His variant in CDH23 has not been previously reported in individuals w ith hearing loss, but has been identified in 0.03% (1/3864) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs374955091). Although this variant has been seen in the general pop ulation, its frequency is not high enough to rule out a pathogenic role. Computa tional prediction tools and conservation analyses suggest that the Arg724His var iant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the Arg724His variant is uncertain - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at