rs2870820

Positions:

• chr12-68808546-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002392.6(MDM2):​c.14+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,610,530 control chromosomes in the GnomAD database, including 115,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (8077 hom., cov: 33)
  • Exomes 𝑓: 0.38 (107292 hom.)
• Consequence: MDM2 NM_002392.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.393

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-68808546-C-T is Benign according to our data. Variant chr12-68808546-C-T is described in ClinVar as [Benign]. Clinvar id is 695297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MDM2	NM_002392.6	c.14+55C>T		intron_variant		ENST00000258149.11
MDM2	NM_001145339.2	c.14+55C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MDM2	ENST00000258149.11	c.14+55C>T		intron_variant		1	NM_002392.6

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45060 AN: 152078 Hom.: 8077 Cov.: 33

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.375 AC: 547128 AN: 1458334 Hom.: 107292 AF XY: 0.372 AC XY: 269501 AN XY: 725202

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.296 AC: 45065 AN: 152196 Hom.: 8077 Cov.: 33 AF XY: 0.294 AC XY: 21846 AN XY: 74394

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.296

Alfa AF: 0.349 Hom.: 1691

Bravo AF: 0.274

Asia WGS AF: 0.269 AC: 933 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Accelerated tumor formation, susceptibility to Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 01, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.9
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs2870820; hg19: chr12-69202326; COSMIC: COSV50699381; COSMIC: COSV50699381;