rs371212430
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_022124.6(CDH23):c.1227G>A(p.Ala409=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,613,528 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 2 hom. )
Consequence
CDH23
NM_022124.6 synonymous
NM_022124.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.26
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 10-71645917-G-A is Benign according to our data. Variant chr10-71645917-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71645917-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-4.26 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.1227G>A | p.Ala409= | synonymous_variant | 13/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.1227G>A | p.Ala409= | synonymous_variant | 13/32 | ||
CDH23 | NM_001171931.2 | c.1227G>A | p.Ala409= | synonymous_variant | 13/26 | ||
CDH23 | NM_052836.4 | c.1227G>A | p.Ala409= | synonymous_variant | 13/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.1227G>A | p.Ala409= | synonymous_variant | 13/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000431 AC: 107AN: 248528Hom.: 0 AF XY: 0.000489 AC XY: 66AN XY: 134898
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GnomAD4 exome AF: 0.000229 AC: 335AN: 1461180Hom.: 2 Cov.: 32 AF XY: 0.000301 AC XY: 219AN XY: 726852
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Ala409Ala in Exon 13 of CDH23: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1/3360 African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS). - |
CDH23-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 19, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at