rs143993990
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_022124.6(CDH23):c.5419G>A(p.Val1807Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000589 in 1,613,942 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. V1807V) has been classified as Likely benign.
Frequency
Consequence
NM_022124.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.5419G>A | p.Val1807Met | missense_variant | 42/70 | ENST00000224721.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.5419G>A | p.Val1807Met | missense_variant | 42/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00251 AC: 382AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000690 AC: 172AN: 249164Hom.: 1 AF XY: 0.000636 AC XY: 86AN XY: 135184
GnomAD4 exome AF: 0.000389 AC: 568AN: 1461610Hom.: 8 Cov.: 32 AF XY: 0.000393 AC XY: 286AN XY: 727104
GnomAD4 genome AF: 0.00251 AC: 382AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.00260 AC XY: 194AN XY: 74498
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 03, 2020 | This variant is associated with the following publications: (PMID: 22899989, 17850630, 25587757, 22443853) - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 31, 2016 | Val1807Met in Exon 42 of CDH23: This variant is not expected to have clinical si gnificance because it has been identified in 0.7% (72/9790) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs143993990). - |
CDH23-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 16, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at