rs376098894
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_022124.6(CDH23):c.9087G>A(p.Gln3029Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000446 in 1,613,762 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00025 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
CDH23
NM_022124.6 synonymous
NM_022124.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.11
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 Likely_benign. Variant got -5 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
Variant 10-71811324-G-A is Benign according to our data. Variant chr10-71811324-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 178312.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.9087G>A | p.Gln3029Gln | synonymous_variant | 63/70 | ENST00000224721.12 | NP_071407.4 | |
CDH23 | NM_001171933.1 | c.2367G>A | p.Gln789Gln | synonymous_variant | 16/23 | NP_001165404.1 | ||
CDH23 | NM_001171934.1 | c.2367G>A | p.Gln789Gln | synonymous_variant | 16/22 | NP_001165405.1 | ||
LOC124902446 | XR_007062185.1 | n.1267+168C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.9087G>A | p.Gln3029Gln | synonymous_variant | 63/70 | 5 | NM_022124.6 | ENSP00000224721.9 |
Frequencies
GnomAD3 genomes AF: 0.000250 AC: 38AN: 152084Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249018Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135132
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461678Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727114
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GnomAD4 genome AF: 0.000250 AC: 38AN: 152084Hom.: 0 Cov.: 31 AF XY: 0.000215 AC XY: 16AN XY: 74292
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 13, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2024 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Gln3029Gln in Exon 63 of CDH23: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.1% (2/3444) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). - |
Computational scores
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BayesDel_noAF
Benign
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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