rs727504694
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_022124.6(CDH23):c.6718G>A(p.Val2240Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V2240L) has been classified 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.6718G>A | p.Val2240Ile | missense_variant | 49/70 | ENST00000224721.12 | |
CDH23 | NM_001171933.1 | c.-3G>A | 5_prime_UTR_variant | 2/23 | |||
CDH23 | NM_001171934.1 | c.-3G>A | 5_prime_UTR_variant | 2/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.6718G>A | p.Val2240Ile | missense_variant | 49/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247548Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134292
GnomAD4 exome AF: 0.00000618 AC: 9AN: 1457416Hom.: 0 Cov.: 29 AF XY: 0.00000690 AC XY: 5AN XY: 725136
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
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 | Sep 08, 2013 | The Val2240Ile variant in CDH23 has not been reported in individuals with hearin g loss or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide s trong support for or against an impact to the protein. In summary, additional in formation is needed to fully assess the clinical significance of the Val2240Ile variant. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 24, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at