11-119372712-C-T

Position:

chr11-119372712-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_004205.5(USP2):c.769G>A(p.Gly257Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000257 in 1,518,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

USP2
NM_004205.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.187

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 links:

USP2-AS1 (HGNC:):

USP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015189886).

BP6

Variant 11-119372712-C-T is Benign according to our data. Variant chr11-119372712-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2209602.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP2	NM_004205.5 linkuse as main transcript	c.769G>A	p.Gly257Ser	missense_variant	2/13	ENST00000260187.7	NP_004196.4	O75604-1
USP2	XM_005271721.6 linkuse as main transcript	c.769G>A	p.Gly257Ser	missense_variant	2/13		XP_005271778.1	O75604-1
USP2	XM_005271722.3 linkuse as main transcript	c.769G>A	p.Gly257Ser	missense_variant	2/13		XP_005271779.1	O75604-1
USP2	NM_001243759.2 linkuse as main transcript	c.45+8761G>A		intron_variant			NP_001230688.1	O75604-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP2	ENST00000260187.7 linkuse as main transcript	c.769G>A	p.Gly257Ser	missense_variant	2/13	1	NM_004205.5	ENSP00000260187.2		O75604-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000287

AC:

AN:

174292

Hom.:

AF XY:

0.0000435

AC XY:

AN XY:

91974

show subpopulations

Gnomad AFR exome

AF:

0.0000661

Gnomad AMR exome

AF:

0.00

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:

0.0000468

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1366562

Hom.:

Cov.:

AF XY:

0.0000254

AC XY:

AN XY:

670446

show subpopulations

Gnomad4 AFR exome

AF:

0.0000661

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000602

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000568

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000935

Gnomad4 OTH exome

AF:

0.0000889

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000251

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.4

DANN

Benign

0.87

DEOGEN2

Benign

0.036

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.15

M_CAP

Benign

0.0063

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.34

PrimateAI

Benign

0.33

PROVEAN

Benign

0.69

REVEL

Benign

0.041

Sift

Benign

0.85

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.022

MutPred

0.21

Gain of phosphorylation at G257 (P = 0.0062);

MVP

0.16

MPC

0.30

ClinPred

0.014

GERP RS

1.5

Varity_R

0.034

gMVP

0.17

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