Variant chr2-158123758-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000005756.5(UPP2):c.674G>T(p.Arg225Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,613,786 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00078 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

UPP2
ENST00000005756.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

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 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=0.0989961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UPP2	NM_173355.4 linkuse as main transcript	c.674G>T	p.Arg225Leu	missense_variant	6/7	ENST00000005756.5	NP_775491.1
UPP2	NM_001135098.2 linkuse as main transcript	c.845G>T	p.Arg282Leu	missense_variant	8/9		NP_001128570.1
UPP2	XM_017003484.2 linkuse as main transcript			downstream_gene_variant			XP_016858973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPP2	ENST00000005756.5 linkuse as main transcript	c.674G>T	p.Arg225Leu	missense_variant	6/7	1	NM_173355.4	ENSP00000005756	P1	O95045-1
UPP2	ENST00000605860.5 linkuse as main transcript	c.845G>T	p.Arg282Leu	missense_variant	9/10	5		ENSP00000474090		O95045-2
UPP2	ENST00000460456.1 linkuse as main transcript	n.386G>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000363

AC:

AN:

250638

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

135456

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00587

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000181

AC:

264

AN:

1461442

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

126

AN XY:

727000

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00667

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000781

AC:

119

AN:

152344

Hom.:

Cov.:

AF XY:

0.000859

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000420

Hom.:

Bravo

AF:

0.000816

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Jul 27, 2021

The c.845G>T (p.R282L) alteration is located in exon 8 (coding exon 8) of the UPP2 gene. This alteration results from a G to T substitution at nucleotide position 845, causing the arginine (R) at amino acid position 282 to be replaced by a leucine (L). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

.;D

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.084

MetaRNN

Benign

0.099

T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Pathogenic

3.1

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-6.6

.;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

.;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

.;D

Vest4

0.83

MVP

0.85

MPC

0.78

ClinPred

0.15

GERP RS

4.0

Varity_R

0.85

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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