Genetic Variant UGP2:p.Val143Leu (chr2-63882637-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006759.4(UGP2):c.427G>C(p.Val143Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,569,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

UGP2
NM_006759.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.19

Publications

3 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

UGP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21333128).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006759.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UGP2	NM_006759.4	MANE Select	c.427G>C	p.Val143Leu	missense	Exon 4 of 10	NP_006750.3
UGP2	NM_001001521.2		c.394G>C	p.Val132Leu	missense	Exon 4 of 10	NP_001001521.1	Q16851-2
UGP2	NM_001377524.1		c.394G>C	p.Val132Leu	missense	Exon 5 of 11	NP_001364453.1	A0A140VKE1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UGP2	ENST00000337130.10	TSL:1 MANE Select	c.427G>C	p.Val143Leu	missense	Exon 4 of 10	ENSP00000338703.5	Q16851-1
UGP2	ENST00000394417.7	TSL:1	c.394G>C	p.Val132Leu	missense	Exon 4 of 10	ENSP00000377939.2	Q16851-2
UGP2	ENST00000467648.6	TSL:1	c.394G>C	p.Val132Leu	missense	Exon 5 of 11	ENSP00000420793.2	Q16851-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000498

AC:

AN:

241028

AF XY:

0.0000538

show subpopulations

Gnomad AFR exome

AF:

0.000620

Gnomad AMR exome

AF:

0.0000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000127

AC:

AN:

1417122

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

698096

show subpopulations

African (AFR)

AF:

0.000368

AC:

AN:

32642

American (AMR)

AF:

0.0000474

AC:

AN:

42158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25314

East Asian (EAS)

AF:

0.00

AC:

AN:

38778

South Asian (SAS)

AF:

0.00

AC:

AN:

79782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5594

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1081756

Other (OTH)

AF:

0.0000342

AC:

AN:

58434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000555

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.000178

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.019

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

PhyloP100

8.2

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.29

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.014

Polyphen

0.59

Vest4

0.77

MVP

0.42

MPC

1.3

ClinPred

0.17

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.63

gMVP

0.80

Mutation Taster

=80/20

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over