rs111033467
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_022124.6(CDH23):c.9002G>A(p.Arg3001Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000301 in 1,461,662 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R3001R) has been classified as Likely benign.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.9002G>A | p.Arg3001Gln | missense_variant | 62/70 | ENST00000224721.12 | |
LOC124902446 | XR_007062185.1 | n.1399C>T | non_coding_transcript_exon_variant | 2/2 | |||
CDH23 | NM_001171933.1 | c.2282G>A | p.Arg761Gln | missense_variant | 15/23 | ||
CDH23 | NM_001171934.1 | c.2282G>A | p.Arg761Gln | missense_variant | 15/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.9002G>A | p.Arg3001Gln | missense_variant | 62/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249256Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135240
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461662Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727112
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 27, 2011 | The Arg3001Gln in CDH23 has not been reported in the literature nor previously i dentified by our laboratory in any other families. Computational analyses (bioch emical amino acid properties, homology, PolyPhen2, SIFT, AlignGVGD) do not provi de strong support for or against pathogenicity. This variant has now been identi fied in this individual and her sibling, both of whom have sensorineural hearing loss. Although this finding is consistent with a causative role, because two si blings have a 50% chance of sharing any variant by chance, the clinical signific ance of this variant still cannot be determined at this time. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 29, 2022 | Variant summary: CDH23 c.9002G>A (p.Arg3001Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 249256 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.9002G>A in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Autosomal recessive nonsyndromic hearing loss 12;C1832845:Usher syndrome type 1D;C4539685:Pituitary adenoma 5, multiple types Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 29, 2021 | - - |
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 | Invitae | May 15, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 3001 of the CDH23 protein (p.Arg3001Gln). This variant is present in population databases (rs111033467, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 46064). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at