Variant 2-158115152-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_173355.4(UPP2):c.232A>C(p.Met78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00115 in 1,613,812 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0054 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00071 ( 3 hom. )

Consequence

UPP2
NM_173355.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071976483).

BP6

Variant 2-158115152-A-C is Benign according to our data. Variant chr2-158115152-A-C is described in ClinVar as [Benign]. Clinvar id is 778012.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0054 (822/152236) while in subpopulation AFR AF= 0.0177 (734/41548). AF 95% confidence interval is 0.0166. There are 7 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UPP2	NM_173355.4 linkuse as main transcript	c.232A>C	p.Met78Leu	missense_variant	3/7	ENST00000005756.5
UPP2	NM_001135098.2 linkuse as main transcript	c.403A>C	p.Met135Leu	missense_variant	5/9
UPP2	XM_017003484.2 linkuse as main transcript	c.232A>C	p.Met78Leu	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPP2	ENST00000005756.5 linkuse as main transcript	c.232A>C	p.Met78Leu	missense_variant	3/7	1	NM_173355.4	P1	O95045-1
UPP2	ENST00000605860.5 linkuse as main transcript	c.403A>C	p.Met135Leu	missense_variant	6/10	5			O95045-2
UPP2	ENST00000460456.1 linkuse as main transcript	n.377-8597A>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00539

AC:

820

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00162

AC:

407

AN:

250808

Hom.:

AF XY:

0.00114

AC XY:

154

AN XY:

135532

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.000609

Gnomad ASJ exome

AF:

0.00586

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000709

AC:

1036

AN:

1461576

Hom.:

Cov.:

AF XY:

0.000626

AC XY:

455

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00666

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00540

AC:

822

AN:

152236

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

402

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00646

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00177

AC:

215

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000437

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.71

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.21

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.37

Sift4G

Benign

0.78

T;T

Polyphen

0.0010

.;B

Vest4

0.47

MutPred

0.26

.;Loss of methylation at K80 (P = 0.1043);

MVP

0.19

MPC

0.16

ClinPred

0.0036

GERP RS

4.5

Varity_R

0.24

gMVP

0.57

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

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