rs751220612
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_022124.6(CDH23):c.1450-10G>A 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 0.0000378 in 1,613,370 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_022124.6 splice_polypyrimidine_tract, intron
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.1450-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000224721.12 | |||
CDH23 | NM_001171930.2 | c.1450-10G>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
CDH23 | NM_001171931.2 | c.1450-10G>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.1450-10G>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 249092Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135158
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461158Hom.: 0 Cov.: 29 AF XY: 0.0000413 AC XY: 30AN XY: 726884
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74362
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 18, 2016 | The c.1450-10G>A variant in CDH23 has not been previously reported in individual s with hearing loss or Usher syndrome. It has been identified in 4/66404 Europe an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs751220612); however, its frequency is not high enough to rule out a pathogenic role. This variant is located in the 3' splice region. Computat ional tools do not suggest an impact to splicing. However, this information is n ot predictive enough to rule out pathogenicity. In summary, the clinical signifi cance of the c.1450-10G>A variant is uncertain. - |
Usher syndrome type 1D Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City | Sep 26, 2019 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at