rs150768738

Variant names:

• chr11-119357206-G-A
• rs150768738
• NM_004205.5:c.1711C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-119357206-G-A
• chr11-119357206-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 13/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.20
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16867787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004205.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP2	NM_004205.5	MANE Select	c.1711C>T	p.His571Tyr	missense	Exon 12 of 13	NP_004196.4
	USP2	NM_171997.3		c.1084C>T	p.His362Tyr	missense	Exon 11 of 12	NP_741994.1	O75604-4
	USP2	NM_001243759.2		c.982C>T	p.His328Tyr	missense	Exon 11 of 12	NP_001230688.1	O75604-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP2	ENST00000260187.7	TSL:1 MANE Select	c.1711C>T	p.His571Tyr	missense	Exon 12 of 13	ENSP00000260187.2	O75604-1
	USP2	ENST00000525735.1	TSL:1	c.1084C>T	p.His362Tyr	missense	Exon 11 of 12	ENSP00000436952.1	O75604-4
	USP2	ENST00000455332.6	TSL:1	c.982C>T	p.His328Tyr	missense	Exon 11 of 12	ENSP00000407842.2	O75604-3

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152044 Hom.: 0 Cov.: 30

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

GnomAD2 exomes AF: 0.0000640 AC: 16 AN: 250184 AF XY: 0.0000738

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 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.: 1 Cov.: 41 AF XY: 0.000320 AC XY: 233 AN XY: 727108

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000411 AC: 457 AN: 1111986

Other (OTH) AF: 0.000132 AC: 8 AN: 60392

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152044 Hom.: 0 Cov.: 30 AF XY: 0.000121 AC XY: 9 AN XY: 74246

African (AFR) AF: 0.000169 AC: 7 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000187 Hom.: 0

Bravo AF: 0.0000793

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	-0.66	N
PhyloP100		6.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Benign	0.57	T
Polyphen		0.078	B
Vest4		0.36
MVP		0.32
MPC		0.48
ClinPred		0.094	T
GERP RS		5.6
Varity_R		0.64
gMVP		0.30
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs150768738; hg19: chr11-119227916;