11-119364694-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USP2	NM_004205.5	c.775-4460G>A		intron_variant		ENST00000260187.7
USP2	NM_001243759.2	c.46-4460G>A		intron_variant
USP2	XM_005271721.6	c.775-4460G>A		intron_variant
USP2	XM_005271722.3	c.775-4460G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP2	ENST00000260187.7	c.775-4460G>A		intron_variant		1	NM_004205.5
USP2-AS1	ENST00000706409.1	n.251+7977C>T		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.575

Alfa AF: 0.542 Hom.: 36517

Bravo AF: 0.535

Asia WGS AF: 0.720 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.2
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs2195525; hg19: chr11-119235404;