rs185105210
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_022124.6(CDH23):c.1185C>T(p.Ser395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,613,460 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 2 hom. )
Consequence
CDH23
NM_022124.6 synonymous
NM_022124.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.106
Genes affected
CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
?
Variant 10-71645875-C-T is Benign according to our data. Variant chr10-71645875-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 45863.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=1}.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AD,AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.1185C>T | p.Ser395= | synonymous_variant | 13/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.1185C>T | p.Ser395= | synonymous_variant | 13/32 | ||
CDH23 | NM_001171931.2 | c.1185C>T | p.Ser395= | synonymous_variant | 13/26 | ||
CDH23 | NM_052836.4 | c.1185C>T | p.Ser395= | synonymous_variant | 13/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.1185C>T | p.Ser395= | synonymous_variant | 13/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000591 AC: 90AN: 152208Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000173 AC: 43AN: 248846Hom.: 0 AF XY: 0.000170 AC XY: 23AN XY: 135018
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GnomAD4 exome AF: 0.000114 AC: 167AN: 1461134Hom.: 2 Cov.: 32 AF XY: 0.000125 AC XY: 91AN XY: 726730
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GnomAD4 genome ? AF: 0.000611 AC: 93AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | CDH23: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 11, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 11, 2020 | This variant is associated with the following publications: (PMID: 18429043) - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 07, 2011 | p.Ser395Ser in exon 13 of CDH23: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located near a splice junction and has been identified in 0.2% (19/9594) of African chromoso mes by the Exome Aggregation Consortium (http://exac.broadinstitute.org/variant/ ; rs185105210). In addition, this variant is listed as presumed neutral in one publication (Oshima 2008). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at