rs1553288362
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024529.5(CDC73):c.1052delC(p.Pro351GlnfsTer13) 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 (★). Synonymous variant affecting the same amino acid position (i.e. P351P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_024529.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.98e-7 AC: 1AN: 1432600Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 710326
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Parathyroid carcinoma Pathogenic:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at