chr11-119372792-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_004205.5(USP2):c.689C>T(p.Pro230Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000751 in 1,599,712 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0036 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00045 ( 4 hom. )
Consequence
USP2
NM_004205.5 missense
NM_004205.5 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 3.79
Genes affected
USP2 (HGNC:12618): (ubiquitin specific peptidase 2) This gene encodes a member of the family of de-ubiquitinating enzymes, which belongs to the peptidase C19 superfamily. The encoded protein is a ubiquitin-specific protease which is required for TNF-alpha (tumor necrosis factor alpha) -induced NF-kB (nuclear factor kB) signaling. This protein deubiquitinates polyubiquitinated target proteins such as fatty acid synthase, murine double minute 2 (MDM2), MDM4/MDMX and cyclin D1. MDM2 and MDM4 are negative regulators of the p53 tumor suppressor and cyclin D1 is required for cell cycle G1/S transition. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.005486816).
BP6
Variant 11-119372792-G-A is Benign according to our data. Variant chr11-119372792-G-A is described in ClinVar as [Benign]. Clinvar id is 734837.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
USP2 | NM_004205.5 | c.689C>T | p.Pro230Leu | missense_variant | 2/13 | ENST00000260187.7 | NP_004196.4 | |
USP2 | XM_005271721.6 | c.689C>T | p.Pro230Leu | missense_variant | 2/13 | XP_005271778.1 | ||
USP2 | XM_005271722.3 | c.689C>T | p.Pro230Leu | missense_variant | 2/13 | XP_005271779.1 | ||
USP2 | NM_001243759.2 | c.45+8681C>T | intron_variant | NP_001230688.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
USP2 | ENST00000260187.7 | c.689C>T | p.Pro230Leu | missense_variant | 2/13 | 1 | NM_004205.5 | ENSP00000260187 | ||
USP2-AS1 | ENST00000706409.1 | n.251+16075G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00367 AC: 558AN: 152236Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.000973 AC: 231AN: 237338Hom.: 0 AF XY: 0.000696 AC XY: 89AN XY: 127826
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GnomAD4 exome AF: 0.000446 AC: 645AN: 1447358Hom.: 4 Cov.: 30 AF XY: 0.000406 AC XY: 292AN XY: 719124
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GnomAD4 genome AF: 0.00365 AC: 556AN: 152354Hom.: 3 Cov.: 33 AF XY: 0.00361 AC XY: 269AN XY: 74504
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 18, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at