11-119357206-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004205.5(USP2):c.1711C>T(p.His571Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0003 in 1,613,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

USP2
NM_004205.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

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:48673): (USP2 antisense RNA 1)

USP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16867787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USP2	NM_004205.5 link	c.1711C>T	p.His571Tyr	missense_variant	Exon 12 of 13	ENST00000260187.7	NP_004196.4	O75604-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
USP2	ENST00000260187.7 link	c.1711C>T	p.His571Tyr	missense_variant	Exon 12 of 13	1	NM_004205.5	ENSP00000260187.2	O75604-1
USP2	ENST00000525735.1 link	c.1084C>T	p.His362Tyr	missense_variant	Exon 11 of 12	1		ENSP00000436952.1	O75604-4
USP2	ENST00000455332.6 link	c.982C>T	p.His328Tyr	missense_variant	Exon 11 of 12	1		ENSP00000407842.2	O75604-3
USP2-AS1	ENST00000706409.1 link	n.251+489G>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000640

AC:

AN:

250184

Hom.:

AF XY:

0.0000738

AC XY:

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.000124

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000319

AC:

466

AN:

1461634

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

233

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000411

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000118

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000175

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1711C>T (p.H571Y) alteration is located in exon 12 (coding exon 11) of the USP2 gene. This alteration results from a C to T substitution at nucleotide position 1711, causing the histidine (H) at amino acid position 571 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.18

.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

-0.66

.;N;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.13

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.078, 0.0050

.;B;B

Vest4

0.36

MVP

0.32

MPC

0.48

ClinPred

0.094

GERP RS

5.6

Varity_R

0.64

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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