rs397517318
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_022124.6(CDH23):c.2840T>A(p.Val947Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,484 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V947L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.2840T>A | p.Val947Glu | missense_variant | 25/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.2840T>A | p.Val947Glu | missense_variant | 25/32 | ||
CDH23 | NM_001171931.2 | c.2840T>A | p.Val947Glu | missense_variant | 25/26 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.2840T>A | p.Val947Glu | missense_variant | 25/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151944Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247076Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134830
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460540Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726582
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151944Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74224
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 | Jan 10, 2012 | The Val947Glu variant in CDH23 has not been reported in the literature nor ident ified by our laboratory. Computational analyses (biochemical amino acid properti es, homology, PolyPhen2, SIFT, AlignGVGD) do not provide strong support for or a gainst pathogenicity. In summary, the clinical significance of this variant cann ot be determined with certainty at this time. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 12, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on 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