12-68809221-A-C
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002392.6(MDM2):c.28A>C(p.Thr10Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
MDM2
NM_002392.6 missense
NM_002392.6 missense
Scores
8
11
Clinical Significance
Conservation
PhyloP100: 5.41
Genes affected
MDM2 (HGNC:6973): (MDM2 proto-oncogene) This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29838985).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Accelerated tumor formation, susceptibility to;C5231460:Lessel-kubisch syndrome Uncertain:1
Jan 14, 2024
Fulgent Genetics, Fulgent Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;D;T;.;.;.;.;T;.;.;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;.;.;.;D;D;D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;L;.;.;.;.;.;.;L;L;.;.;L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;D;D;D;D;D;N;N;N;N;D;N;N
REVEL
Benign
Sift
Uncertain
D;T;D;D;D;D;D;D;.;D;D;D;T;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;T;D;D;D;D
Polyphen
P;.;.;P;P;.;.;.;.;.;.;D;.;.;.;.;.
Vest4
MutPred
0.27
.;Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);.;Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);Gain of catalytic residue at C2 (P = 0.0026);
MVP
ClinPred
D
GERP RS
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
Publications
No publications associated with this variant yet.