11-119364694-C-T

Variant names:

• chr11-119364694-C-T
• rs2195525
• NM_004205.5:c.775-4460G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004205.5(USP2):​c.775-4460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,018 control chromosomes in the GnomAD database, including 22,007 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (22007 hom., cov: 32)
• Consequence: USP2 NM_004205.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

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.775-4460G>A		intron	N/A	NP_004196.4
	USP2	NM_001243759.2		c.46-4460G>A		intron	N/A	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.775-4460G>A		intron	N/A	ENSP00000260187.2	O75604-1
	USP2	ENST00000455332.6	TSL:1	c.46-4460G>A		intron	N/A	ENSP00000407842.2	O75604-3
	USP2	ENST00000876643.1		c.775-4460G>A		intron	N/A	ENSP00000546702.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80593 AN: 151900 Hom.: 21985 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.573

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.531 AC: 80664 AN: 152018 Hom.: 22007 Cov.: 32 AF XY: 0.539 AC XY: 40020 AN XY: 74308

African (AFR) AF: 0.442 AC: 18329 AN: 41446

American (AMR) AF: 0.636 AC: 9714 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3468

East Asian (EAS) AF: 0.808 AC: 4184 AN: 5176

South Asian (SAS) AF: 0.642 AC: 3093 AN: 4818

European-Finnish (FIN) AF: 0.534 AC: 5632 AN: 10544

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35883 AN: 67966

Other (OTH) AF: 0.575 AC: 1214 AN: 2112

Alfa AF: 0.538 Hom.: 88658

Bravo AF: 0.535

Asia WGS AF: 0.720 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.74
PhyloP100		-0.31
PromoterAI		0.065	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2195525; hg19: chr11-119235404;