Variant 12-68808800-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002392.6(MDM2):c.14+309T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 629,096 control chromosomes in the GnomAD database, including 37,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9408 hom., cov: 32)

Exomes 𝑓: 0.34 ( 28346 hom. )

Consequence

MDM2
NM_002392.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -1.76

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 12-68808800-T-G is Benign according to our data. Variant chr12-68808800-T-G is described in ClinVar as [Benign]. Clinvar id is 13904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MDM2	NM_002392.6 linkuse as main transcript	c.14+309T>G		intron_variant		ENST00000258149.11	NP_002383.2
MDM2	NM_001145339.2 linkuse as main transcript	c.14+309T>G		intron_variant			NP_001138811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MDM2	ENST00000258149.11 linkuse as main transcript	c.14+309T>G		intron_variant		1	NM_002392.6	ENSP00000258149		Q00987-11

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48654

AN:

151752

Hom.:

9411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.534

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.364

GnomAD4 exome

AF:

0.336

AC:

160269

AN:

477226

Hom.:

28346

AF XY:

0.338

AC XY:

75832

AN XY:

224100

show subpopulations

Gnomad4 AFR exome

AF:

0.0730

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.506

Gnomad4 EAS exome

AF:

0.513

Gnomad4 SAS exome

AF:

0.529

Gnomad4 FIN exome

AF:

0.411

Gnomad4 NFE exome

AF:

0.334

Gnomad4 OTH exome

AF:

0.365

GnomAD4 genome

AF:

0.320

AC:

48647

AN:

151870

Hom.:

9408

Cov.:

AF XY:

0.330

AC XY:

24522

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.512

Gnomad4 EAS

AF:

0.534

Gnomad4 SAS

AF:

0.535

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.363

Alfa

AF:

0.319

Hom.:

2658

Bravo

AF:

0.315

Asia WGS

AF:

0.480

AC:

1670

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Accelerated tumor formation, susceptibility to

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 06, 2023	- -
risk factor, no assertion criteria provided	literature only	OMIM	Oct 01, 2009	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.96

DANN

Benign

0.56

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.4

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over