rs397517312
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_022124.6(CDH23):c.1866C>T(p.Ser622=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,611,484 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
CDH23
NM_022124.6 synonymous
NM_022124.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.07
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 -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 10-71682452-C-T is Benign according to our data. Variant chr10-71682452-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 45884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.07 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.1866C>T | p.Ser622= | synonymous_variant | 18/70 | ENST00000224721.12 | NP_071407.4 | |
CDH23 | NM_001171930.2 | c.1866C>T | p.Ser622= | synonymous_variant | 18/32 | NP_001165401.1 | ||
CDH23 | NM_001171931.2 | c.1866C>T | p.Ser622= | synonymous_variant | 18/26 | NP_001165402.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.1866C>T | p.Ser622= | synonymous_variant | 18/70 | 5 | NM_022124.6 | ENSP00000224721 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152158Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000327 AC: 8AN: 244424Hom.: 0 AF XY: 0.0000377 AC XY: 5AN XY: 132736
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459326Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 725698
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74330
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 10, 2013 | Ser622Ser in exon 18 of CDH23: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 11, 2023 | - - |
Computational scores
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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