chr10-71793582-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_022124.6(CDH23):c.6654C>A(p.Asp2218Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,610,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 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. D2218D) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.6654C>A | p.Asp2218Glu | missense_variant | 48/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.6654C>A | p.Asp2218Glu | missense_variant | 48/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152148Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000930 AC: 23AN: 247242Hom.: 0 AF XY: 0.0000671 AC XY: 9AN XY: 134224
GnomAD4 exome AF: 0.0000302 AC: 44AN: 1458024Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 724608
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 26, 2015 | The p.Asp2218Glu variant in CDH23 has not been previously reported in individual s with hearing loss, but has been identified in 0.1% (9/8502) of East Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs537236734). Although this variant has been seen in the general popula tion, its frequency is not high enough to rule out a pathogenic role. Computatio nal prediction tools and conservation analysis suggest that this variant may imp act the protein, though this information is not predictive enough to determine p athogenicity. In summary, the clinical significance of the p.Asp2218Glu variant is uncertain. - |
Autosomal recessive nonsyndromic hearing loss 12;C1832845:Usher syndrome type 1D;C4539685:Pituitary adenoma 5, multiple types Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 03, 2022 | - - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at