Variant 11-119356918-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004205.5(USP2):c.1735A>G(p.Thr579Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000356 in 1,406,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

USP2
NM_004205.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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:

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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=0.21371448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP2	NM_004205.5 link	c.1735A>G	p.Thr579Ala	missense_variant	13/13	ENST00000260187.7	NP_004196.4	O75604-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
USP2	ENST00000260187.7 link	c.1735A>G	p.Thr579Ala	missense_variant	13/13	1	NM_004205.5	ENSP00000260187.2	O75604-1
USP2	ENST00000525735.1 link	c.1108A>G	p.Thr370Ala	missense_variant	12/12	1		ENSP00000436952.1	O75604-4
USP2	ENST00000455332.6 link	c.1006A>G	p.Thr336Ala	missense_variant	12/12	1		ENSP00000407842.2	O75604-3
USP2-AS1	ENST00000706409.1 link	n.251+201T>C		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000356

AC:

AN:

1406420

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

694288

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000461

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2024

The c.1735A>G (p.T579A) alteration is located in exon 13 (coding exon 12) of the USP2 gene. This alteration results from a A to G substitution at nucleotide position 1735, causing the threonine (T) at amino acid position 579 to be replaced by an alanine (A). 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

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.083

.;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.0087

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;M;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.073

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.0030, 0.046

.;B;B

Vest4

0.22

MutPred

0.40

.;Loss of glycosylation at T579 (P = 0.0222);.;

MVP

0.44

MPC

0.31

ClinPred

0.85

GERP RS

3.3

Varity_R

0.35

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over