Variant 2-158102092-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173355.4(UPP2):c.29G>A(p.Arg10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R10S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

UPP2
NM_173355.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.02

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037067622).

BP6

Variant 2-158102092-G-A is Benign according to our data. Variant chr2-158102092-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3186843.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 link	c.29G>A	p.Arg10Lys	missense_variant	1/7	ENST00000005756.5	NP_775491.1
UPP2	NM_001135098.2 link	c.200G>A	p.Arg67Lys	missense_variant	3/9		NP_001128570.1
UPP2	XM_017003484.2 link	c.29G>A	p.Arg10Lys	missense_variant	1/6		XP_016858973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UPP2	ENST00000005756.5 link	c.29G>A	p.Arg10Lys	missense_variant	1/7	1	NM_173355.4	ENSP00000005756.5	O95045-1
UPP2	ENST00000605860.5 link	c.200G>A	p.Arg67Lys	missense_variant	4/10	5		ENSP00000474090.1	O95045-2
UPP2	ENST00000460456.1 link	n.225G>A		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 15, 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

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

DANN

Benign

0.45

DEOGEN2

Benign

0.013

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L

PrimateAI

Benign

0.25

PROVEAN

Benign

0.35

.;N

REVEL

Benign

0.012

Sift

Benign

0.99

.;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

.;B

Vest4

0.030

MutPred

0.21

.;Gain of ubiquitination at R10 (P = 0.0054);

MVP

0.18

MPC

0.17

ClinPred

0.035

GERP RS

1.1

Varity_R

0.036

gMVP

0.11

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