2-63884063-G-T

Position:

• chr2-63884063-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006759.4(UGP2):​c.545G>T​(p.Arg182Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,460,566 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: UGP2 NM_006759.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.69

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGP2	NM_006759.4	c.545G>T	p.Arg182Leu	missense_variant	5/10	ENST00000337130.10	NP_006750.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGP2	ENST00000337130.10	c.545G>T	p.Arg182Leu	missense_variant	5/10	1	NM_006759.4	ENSP00000338703.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460566 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 726524

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.545G>T (p.R182L) alteration is located in exon 5 (coding exon 5) of the UGP2 gene. This alteration results from a G to T substitution at nucleotide position 545, causing the arginine (R) at amino acid position 182 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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;.;T;T;.;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	.;D;D;D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	.;.;M;.;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D;D;.
REVEL	Uncertain	0.35
Sift	Benign	0.030	D;D;D;D;D;D;.
Sift4G	Benign	0.17	T;T;T;D;T;T;T
Polyphen		0.73, 0.83	.;.;P;.;P;.;.
Vest4		0.74
MutPred		0.54		.;.;.;.;Loss of MoRF binding (P = 0.0209);.;.;
MVP		0.52
MPC		0.66
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.56
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-64111197;