rs371872394
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_022124.6(CDH23):c.7055-15G>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 0.00000207 in 1,452,612 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.7055-15G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000224721.12 | |||
CDH23 | NM_001171933.1 | c.335-15G>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
CDH23 | NM_001171934.1 | c.335-15G>A | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.7055-15G>A | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152210Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245448Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133176
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1452612Hom.: 0 Cov.: 34 AF XY: 0.00000416 AC XY: 3AN XY: 721124
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74480
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 | Aug 10, 2017 | Variant classified as Uncertain Significance - Favor Benign. The c.7055-15G>A va riant in CDH23 has not been previously reported in individuals with hearing loss , but has been identified in 1/109340 European chromosomes by the Genome Aggrega tion Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs371872394). Alt hough this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant is located in the 3' sp lice region. Computational tools do not suggest an impact to splicing. Furthermo re, this nucleotide is not conserved with two mammals (prairie vole and ferret) having an adenine (A) at this position. However, this information is not predict ive enough to rule out pathogenicity. In summary, while the clinical significanc e of the c.7055-15G>A variant is uncertain, the splicing and conservation data s uggest it is more likely to be benign. - |
Usher syndrome type 1D Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Autosomal recessive nonsyndromic hearing loss 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 10, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at