rs375900265
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_022124.6(CDH23):c.6637G>A(p.Gly2213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,612,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G2213G) has been classified as Likely benign.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.6637G>A | p.Gly2213Ser | missense_variant | 48/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.6637G>A | p.Gly2213Ser | missense_variant | 48/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152028Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000133 AC: 33AN: 248258Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 134742
GnomAD4 exome AF: 0.000148 AC: 216AN: 1460658Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 118AN XY: 726478
GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152028Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9AN XY: 74250
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | The c.6637G>A (p.G2213S) alteration is located in exon 48 (coding exon 47) of the CDH23 gene. This alteration results from a G to A substitution at nucleotide position 6637, causing the glycine (G) at amino acid position 2213 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 11, 2013 | Gly2213Ser in Exon 48 of CDH23: This variant is not expected to have clinical s ignificance because the glycine (Gly) residue at position 2213 is not conserved through species, with many mammals having a serine (Ser). In addition, this var iant has been identified in 0.01% (1/8522) of European American chromosomes by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs37 5900265). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at