Genetic Variant NM_002392.6:c.85G>C (chr12-68809278-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002392.6(MDM2):c.85G>C(p.Glu29Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MDM2
NM_002392.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.19

Variant links:

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]

MDM2 links:

Genome browser will be placed here

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=0.26838222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MDM2	NM_002392.6 link	c.85G>C	p.Glu29Gln	missense_variant	Exon 2 of 11	ENST00000258149.11	NP_002383.2	Q00987-11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11 link	c.85G>C	p.Glu29Gln	missense_variant	Exon 2 of 11	1	NM_002392.6	ENSP00000258149.6		Q00987-11

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;T;T;T;D;T;.;.;.;.;T;.;.;.;.;.;T;T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.93

D;D;D;D;D;D;D;D;.;.;.;D;D;D;.;D;D;.;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.27

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.3

.;.;.;.;M;.;.;.;.;.;.;M;M;.;.;M;.;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.52

.;N;N;N;N;N;N;N;N;N;N;N;N;N;D;N;N;N;D

REVEL

Benign

0.094

Sift

Benign

0.10

.;T;D;D;D;D;D;D;.;T;D;D;T;T;D;D;T;T;.

Sift4G

Benign

0.15

T;T;D;T;T;D;T;T;T;D;D;D;T;D;D;D;T;T;D

Polyphen

0.94

P;.;D;P;P;.;.;.;.;.;D;D;D;D;.;D;.;.;.

Vest4

0.26

MutPred

0.22

.;Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);.;Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);Gain of catalytic residue at Q18 (P = 0.0991);.;.;

MVP

0.70

ClinPred

0.90

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.67

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over