10-71803233-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_022124.6(CDH23):c.7685C>T(p.Ser2562Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000262 in 1,603,208 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. S2562S) has been classified as Likely benign.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.7685C>T | p.Ser2562Leu | missense_variant | 55/70 | ENST00000224721.12 | |
CDH23 | NM_001171933.1 | c.965C>T | p.Ser322Leu | missense_variant | 8/23 | ||
CDH23 | NM_001171934.1 | c.965C>T | p.Ser322Leu | missense_variant | 8/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.7685C>T | p.Ser2562Leu | missense_variant | 55/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152222Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000397 AC: 9AN: 226772Hom.: 0 AF XY: 0.0000406 AC XY: 5AN XY: 123244
GnomAD4 exome AF: 0.0000255 AC: 37AN: 1450868Hom.: 0 Cov.: 34 AF XY: 0.0000250 AC XY: 18AN XY: 720772
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152340Hom.: 0 Cov.: 31 AF XY: 0.0000268 AC XY: 2AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 12, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2562 of the CDH23 protein (p.Ser2562Leu). This variant is present in population databases (rs538435711, gnomAD 0.02%). 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: 498532). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 06, 2016 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 30, 2018 | The p.Ser2562Leu variant in CDH23 has been previously reported by our laboratory in one individual with hearing loss; however, this individual had a likely alte rnate explanation for their hearing loss (compound heterozygous likely pathogeni c variants in LARS2). The p.Ser2562Leu variant has also been identified in 0.02% (6/28768) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.or g) and has been reported in ClinVar (Variation ID 498532). Computational predict ion tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser256 2Leu variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at