rs759201338
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_003672.4(CDC14A):βc.376delTβ(p.Tyr126IlefsTer64) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000143 in 1,612,972 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.000026 ( 0 hom., cov: 32)
Exomes π: 0.000013 ( 0 hom. )
Consequence
CDC14A
NM_003672.4 frameshift
NM_003672.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.31
Genes affected
CDC14A (HGNC:1718): (cell division cycle 14A) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. It is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, suggesting a role in cell cycle control. This protein has been shown to interact with, and dephosphorylate tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in several transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-100424287-CT-C is Pathogenic according to our data. Variant chr1-100424287-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 559437.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-100424287-CT-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251318Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135824
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1460758Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 726784
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74370
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 32 Pathogenic:1
Aug 03, 2018
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at