rs11000008
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS1
The NM_022124.6(CDH23):c.8859C>T(p.Asp2953=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000312 in 1,612,330 control chromosomes in the GnomAD database, including 1 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 0.00040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00030 ( 1 hom. )
Consequence
CDH23
NM_022124.6 synonymous
NM_022124.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.42
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 -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 10-71809956-C-T is Benign according to our data. Variant chr10-71809956-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46057.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Likely_benign=3, Uncertain_significance=1}. Variant chr10-71809956-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.42 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000401 (61/152306) while in subpopulation EAS AF= 0.0106 (55/5182). AF 95% confidence interval is 0.00837. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.8859C>T | p.Asp2953= | synonymous_variant | 61/70 | ENST00000224721.12 | |
LOC124902446 | XR_007062185.1 | n.1937G>A | non_coding_transcript_exon_variant | 2/2 | |||
CDH23 | NM_001171933.1 | c.2139C>T | p.Asp713= | synonymous_variant | 14/23 | ||
CDH23 | NM_001171934.1 | c.2139C>T | p.Asp713= | synonymous_variant | 14/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.8859C>T | p.Asp2953= | synonymous_variant | 61/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000401 AC: 61AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000995 AC: 246AN: 247296Hom.: 0 AF XY: 0.00104 AC XY: 140AN XY: 134350
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GnomAD4 exome AF: 0.000303 AC: 442AN: 1460024Hom.: 1 Cov.: 32 AF XY: 0.000296 AC XY: 215AN XY: 726326
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GnomAD4 genome ? AF: 0.000401 AC: 61AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.000537 AC XY: 40AN XY: 74470
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 11, 2021 | This variant is associated with the following publications: (PMID: 17850630) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | CDH23: BP4, BP7, BS1 - |
Autosomal recessive nonsyndromic hearing loss 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 17, 2015 | p.Asp2953Asp in exon 61 of CDH23: This variant is not expected to have clinical significance because has been identified in 1.3% (111/8568) of East Asian chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs11000008). - |
Usher syndrome type 1D Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Usher syndrome type 1 Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 06, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at