rs769412
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_002392.6(MDM2):āc.1080A>Gā(p.Glu360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0622 in 1,613,782 control chromosomes in the GnomAD database, including 3,502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.074 ( 510 hom., cov: 31)
Exomes š: 0.061 ( 2992 hom. )
Consequence
MDM2
NM_002392.6 synonymous
NM_002392.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.282
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 12-68839435-A-G is Benign according to our data. Variant chr12-68839435-A-G is described in ClinVar as [Benign]. Clinvar id is 1167676.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.282 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MDM2 | NM_002392.6 | c.1080A>G | p.Glu360= | synonymous_variant | 11/11 | ENST00000258149.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MDM2 | ENST00000258149.11 | c.1080A>G | p.Glu360= | synonymous_variant | 11/11 | 1 | NM_002392.6 |
Frequencies
GnomAD3 genomes AF: 0.0739 AC: 11222AN: 151810Hom.: 513 Cov.: 31
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GnomAD3 exomes AF: 0.0548 AC: 13680AN: 249520Hom.: 464 AF XY: 0.0544 AC XY: 7362AN XY: 135376
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GnomAD4 exome AF: 0.0610 AC: 89135AN: 1461854Hom.: 2992 Cov.: 31 AF XY: 0.0607 AC XY: 44176AN XY: 727226
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GnomAD4 genome AF: 0.0739 AC: 11230AN: 151928Hom.: 510 Cov.: 31 AF XY: 0.0719 AC XY: 5336AN XY: 74220
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Accelerated tumor formation, susceptibility to Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Benign
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at