rs149441656
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_022124.6(CDH23):c.4210-14A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,918 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 0.0016 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
CDH23
NM_022124.6 splice_polypyrimidine_tract, intron
NM_022124.6 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.04
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 10-71738484-A-C is Benign according to our data. Variant chr10-71738484-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 227225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd4 at 2 AD,AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.4210-14A>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.4210-14A>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_022124.6 | P1 | |||
CDH23 | ENST00000398792.3 | n.899-14A>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00158 AC: 240AN: 152222Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000377 AC: 94AN: 249242Hom.: 0 AF XY: 0.000244 AC XY: 33AN XY: 135228
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GnomAD4 exome AF: 0.000133 AC: 195AN: 1461578Hom.: 0 Cov.: 31 AF XY: 0.000118 AC XY: 86AN XY: 727076
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GnomAD4 genome ? AF: 0.00161 AC: 246AN: 152340Hom.: 2 Cov.: 33 AF XY: 0.00164 AC XY: 122AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 18, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 21, 2016 | c.4210-14A>C in Intron 34 of CDH23: This variant is not expected to have clinica l significance because it has been identified in 0.4% (43/9800) of African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs149441656). - |
Computational scores
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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