Variant 2-158121469-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_173355.4(UPP2):c.515G>A(p.Arg172Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

UPP2
NM_173355.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0870

Variant links:

Genes affected

UPP2 (HGNC:23061): (uridine phosphorylase 2) Enables deoxyuridine phosphorylase activity; identical protein binding activity; and uridine phosphorylase activity. Involved in dCMP catabolic process and uridine catabolic process. Located in type III intermediate filament. [provided by Alliance of Genome Resources, Apr 2022]

UPP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07654384).

BP6

Variant 2-158121469-G-A is Benign according to our data. Variant chr2-158121469-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2517826.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UPP2	NM_173355.4 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	5/7	ENST00000005756.5	NP_775491.1
UPP2	NM_001135098.2 linkuse as main transcript	c.686G>A	p.Arg229Gln	missense_variant	7/9		NP_001128570.1
UPP2	XM_017003484.2 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	5/6		XP_016858973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPP2	ENST00000005756.5 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	5/7	1	NM_173355.4	ENSP00000005756	P1	O95045-1
UPP2	ENST00000605860.5 linkuse as main transcript	c.686G>A	p.Arg229Gln	missense_variant	8/10	5		ENSP00000474090		O95045-2
UPP2	ENST00000460456.1 linkuse as main transcript	n.377-2280G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251202

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135754

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461380

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.014

DANN

Benign

0.46

DEOGEN2

Benign

0.078

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

-1.0

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.12

.;N

REVEL

Benign

0.22

Sift

Benign

0.46

.;T

Sift4G

Benign

0.43

T;T

Polyphen

0.073

.;B

Vest4

0.072

MutPred

0.23

.;Loss of ubiquitination at K170 (P = 0.063);

MVP

0.42

MPC

0.20

ClinPred

0.018

GERP RS

-4.8

Varity_R

0.084

gMVP

0.34

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

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