dbSNP rs1880635622: MDM2:c.15-11T>C (chr12-68809197-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002392.6(MDM2):c.15-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,457,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MDM2
NM_002392.6 intron

Scores

Splicing: ADA: 0.0001086

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.02

Publications

0 publications found

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 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)

MDM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 12-68809197-T-C is Benign according to our data. Variant chr12-68809197-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2908949.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 18 AD,Unknown gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MDM2	NM_002392.6	MANE Select	c.15-11T>C	intron	N/A	NP_002383.2	Q00987-11
MDM2	NM_001367990.1		c.-4-11T>C	intron	N/A	NP_001354919.1	Q00987-1
MDM2	NM_001145337.3		c.-4-11T>C	intron	N/A	NP_001138809.1	A0A0A8KB75

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MDM2	ENST00000258149.11	TSL:1 MANE Select	c.15-11T>C	intron	N/A	ENSP00000258149.6	Q00987-11
MDM2	ENST00000539479.6	TSL:1	c.-4-11T>C	intron	N/A	ENSP00000444430.2	Q00987-1
MDM2	ENST00000258148.11	TSL:1	c.15-11T>C	intron	N/A	ENSP00000258148.7	G3XA89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1457862

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33242

American (AMR)

AF:

0.00

AC:

AN:

43600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25996

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

85354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1110688

Other (OTH)

AF:

0.0000166

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Accelerated tumor formation, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.6

(source)

DANN

Benign

0.90

PhyloP100

-2.0

PromoterAI

-0.0010

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.012

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over