Genetic Variant UGP2:p.Arg3Gly (chr2-63842192-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006759.4(UGP2):c.7A>G(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,596,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

UGP2
NM_006759.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Publications

2 publications found

Variant links:

Genes affected

UGP2 (HGNC:12527): (UDP-glucose pyrophosphorylase 2) The enzyme encoded by this gene is an important intermediary in mammalian carbohydrate interconversions. It transfers a glucose moiety from glucose-1-phosphate to MgUTP and forms UDP-glucose and MgPPi. In liver and muscle tissue, UDP-glucose is a direct precursor of glycogen; in lactating mammary gland it is converted to UDP-galactose which is then converted to lactose. The eukaryotic enzyme has no significant sequence similarity to the prokaryotic enzyme. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

UGP2 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 83
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

UGP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08288044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGP2	NM_006759.4 link	c.7A>G	p.Arg3Gly	missense_variant	Exon 1 of 10	ENST00000337130.10	NP_006750.3	Q16851-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGP2	ENST00000337130.10 link	c.7A>G	p.Arg3Gly	missense_variant	Exon 1 of 10	1	NM_006759.4	ENSP00000338703.5		Q16851-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151416

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000171

AC:

AN:

234574

AF XY:

0.0000314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000991

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000921

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000969

AC:

AN:

1445222

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

719008

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31966

American (AMR)

AF:

0.0000756

AC:

AN:

39660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25532

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00

AC:

AN:

82824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00000993

AC:

AN:

1107598

Other (OTH)

AF:

0.00

AC:

AN:

59592

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151438

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73898

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41268

American (AMR)

AF:

0.0000656

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000437

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jul 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.7A>G (p.R3G) alteration is located in exon 1 (coding exon 1) of the UGP2 gene. This alteration results from a A to G substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 to be replaced by a glycine (G). 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

Benign

0.070

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.030

T;T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.083

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;.

PhyloP100

1.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.23

T;T;T

Sift4G

Pathogenic

0.0

D;T;D

Polyphen

0.0

.;B;.

Vest4

0.29

MVP

0.34

MPC

0.65

ClinPred

0.36

GERP RS

1.9

PromoterAI

0.059

Neutral

(source)

Varity_R

0.078

gMVP

0.34

Mutation Taster

=89/11

polymorphism

(source)

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

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2-63842192-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over