rs28942098
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_ModeratePM2PP5
The NM_024529.5(CDC73):c.3G>A(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CDC73
NM_024529.5 start_lost
NM_024529.5 start_lost
Scores
7
8
1
Clinical Significance
Conservation
PhyloP100: 5.31
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 13 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 43 pathogenic variants. Next in-frame start position is after 177 codons. Genomic position: 193141866. Lost 0.331 part of the original CDS.
PS1
Another start lost variant in NM_024529.5 (CDC73) was described as [Pathogenic] in ClinVar as 489059
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-193122203-G-A is Pathogenic according to our data. Variant chr1-193122203-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3267.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hyperparathyroidism 2 with jaw tumors Pathogenic:1
Dec 01, 2002
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;D;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
PROVEAN
Uncertain
.;D;.
REVEL
Pathogenic
Sift
Uncertain
.;D;.
Sift4G
Pathogenic
.;D;.
Polyphen
D;D;.
Vest4
0.77
MutPred
Gain of catalytic residue at M1 (P = 0.0202);Gain of catalytic residue at M1 (P = 0.0202);Gain of catalytic residue at M1 (P = 0.0202);
MVP
0.95
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at