chr11-119372792-G-A

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

Scores

5
13

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.79
Variant links:
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]
USP2-AS1 (HGNC:48673): (USP2 antisense RNA 1)

Genome browser will be placed here

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
USP2NM_004205.5 linkuse as main transcriptc.689C>T p.Pro230Leu missense_variant 2/13 ENST00000260187.7 NP_004196.4
USP2XM_005271721.6 linkuse as main transcriptc.689C>T p.Pro230Leu missense_variant 2/13 XP_005271778.1
USP2XM_005271722.3 linkuse as main transcriptc.689C>T p.Pro230Leu missense_variant 2/13 XP_005271779.1
USP2NM_001243759.2 linkuse as main transcriptc.45+8681C>T intron_variant NP_001230688.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
USP2ENST00000260187.7 linkuse as main transcriptc.689C>T p.Pro230Leu missense_variant 2/131 NM_004205.5 ENSP00000260187 O75604-1
USP2-AS1ENST00000706409.1 linkuse as main transcriptn.251+16075G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00367
AC:
558
AN:
152236
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0129
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000916
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000973
AC:
231
AN:
237338
Hom.:
0
AF XY:
0.000696
AC XY:
89
AN XY:
127826
show subpopulations
Gnomad AFR exome
AF:
0.0124
Gnomad AMR exome
AF:
0.000664
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000558
Gnomad OTH exome
AF:
0.000520
GnomAD4 exome
AF:
0.000446
AC:
645
AN:
1447358
Hom.:
4
Cov.:
30
AF XY:
0.000406
AC XY:
292
AN XY:
719124
show subpopulations
Gnomad4 AFR exome
AF:
0.0139
Gnomad4 AMR exome
AF:
0.000834
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000240
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000941
Gnomad4 OTH exome
AF:
0.000686
GnomAD4 genome
AF:
0.00365
AC:
556
AN:
152354
Hom.:
3
Cov.:
33
AF XY:
0.00361
AC XY:
269
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0128
Gnomad4 AMR
AF:
0.000915
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000724
Hom.:
0
Bravo
AF:
0.00430
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.0114
AC:
50
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00111
AC:
135
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 18, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T
Eigen
Benign
0.0053
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.84
T
MetaRNN
Benign
0.0055
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.037
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.021
D
Polyphen
0.027
B
Vest4
0.39
MVP
0.43
MPC
0.31
ClinPred
0.043
T
GERP RS
5.4
Varity_R
0.11
gMVP
0.43

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.

Other links and lift over

dbSNP: rs35224356; hg19: chr11-119243502; API