rs1880639329

Variant names:

• chr12-68809225-A-G
• rs1880639329
• NM_002392.6:c.32A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-68809225-A-G
• chr12-68809225-A-C
• chr12-68809225-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002392.6(MDM2):​c.32A>G​(p.Asn11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.756
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Li-Fraumeni syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• lessel-kubisch syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10362974).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002392.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDM2	NM_002392.6	MANE Select	c.32A>G	p.Asn11Ser	missense	Exon 2 of 11	NP_002383.2	Q00987-11
	MDM2	NM_001367990.1		c.14A>G	p.Asn5Ser	missense	Exon 2 of 11	NP_001354919.1	Q00987-1
	MDM2	NM_001145337.3		c.14A>G	p.Asn5Ser	missense	Exon 2 of 11	NP_001138809.1	A0A0A8KB75

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDM2	ENST00000258149.11	TSL:1 MANE Select	c.32A>G	p.Asn11Ser	missense	Exon 2 of 11	ENSP00000258149.6	Q00987-11
	MDM2	ENST00000539479.6	TSL:1	c.14A>G	p.Asn5Ser	missense	Exon 2 of 11	ENSP00000444430.2	Q00987-1
	MDM2	ENST00000350057.9	TSL:1	c.14A>G	p.Asn5Ser	missense	Exon 1 of 9	ENSP00000266624.9	J3KN53

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Accelerated tumor formation, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.76
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.037
Sift	Benign	0.27	T
Sift4G	Benign	0.62	T
Polyphen		0.0040	B
Vest4		0.13
MutPred		0.23		Gain of catalytic residue at C2 (P = 0.0026)
MVP		0.45
ClinPred		0.091	T
GERP RS		3.5
PromoterAI		-0.062	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.087
gMVP		0.51
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1880639329; hg19: chr12-69203005;