rs1553288362
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024529.5(CDC73):c.1052delC(p.Pro351fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000698 in 1,432,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
CDC73
NM_024529.5 frameshift
NM_024529.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.02
Genes affected
CDC73 (HGNC:16783): (cell division cycle 73) This gene encodes a tumor suppressor that is involved in transcriptional and post-transcriptional control pathways. The protein is a component of the the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex. This protein appears to facilitate the association of 3' mRNA processing factors with actively-transcribed chromatin. Mutations in this gene have been linked to hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, and parathyroid carcinoma. [provided by RefSeq, Jul 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 1-193212081-TC-T is Pathogenic according to our data. Variant chr1-193212081-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 462737.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDC73 | NM_024529.5 | c.1052delC | p.Pro351fs | frameshift_variant | 12/17 | ENST00000367435.5 | NP_078805.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDC73 | ENST00000367435.5 | c.1052delC | p.Pro351fs | frameshift_variant | 12/17 | 1 | NM_024529.5 | ENSP00000356405.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432600Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 710326
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Parathyroid carcinoma Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 18, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CDC73 are known to be pathogenic (PMID: 12434154). This variant has not been reported in the literature in individuals with CDC73-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Pro351Glnfs*13) in the CDC73 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at