2-63842200-A-G

Variant names:

• chr2-63842200-A-G
• rs146746356
• NM_006759.4:c.15A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_006759.4(UGP2):​c.15A>G​(p.Val5Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000959 in 1,603,444 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (13 hom.)
• Consequence: UGP2 NM_006759.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.225
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-63842200-A-G is Benign according to our data. Variant chr2-63842200-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1879471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.225 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGP2	NM_006759.4	c.15A>G	p.Val5Val	synonymous_variant	Exon 1 of 10	ENST00000337130.10	NP_006750.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGP2	ENST00000337130.10	c.15A>G	p.Val5Val	synonymous_variant	Exon 1 of 10	1	NM_006759.4	ENSP00000338703.5

Frequencies

GnomAD3 genomes AF: 0.000659 AC: 100 AN: 151746 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00872

Gnomad FIN AF: 0.0000957

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.00140 AC: 338 AN: 240680 AF XY: 0.00188

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.000220

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000235

Gnomad NFE exome AF: 0.000843

Gnomad OTH exome AF: 0.000685

GnomAD4 exome AF: 0.000991 AC: 1439 AN: 1451650 Hom.: 13 Cov.: 35 AF XY: 0.00126 AC XY: 909 AN XY: 722208

African (AFR) AF: 0.0000616 AC: 2 AN: 32476

American (AMR) AF: 0.000265 AC: 11 AN: 41550

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25726

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00925 AC: 779 AN: 84194

European-Finnish (FIN) AF: 0.000189 AC: 10 AN: 53032

Middle Eastern (MID) AF: 0.00650 AC: 37 AN: 5690

European-Non Finnish (NFE) AF: 0.000487 AC: 540 AN: 1109410

Other (OTH) AF: 0.00100 AC: 60 AN: 59902

GnomAD4 genome AF: 0.000652 AC: 99 AN: 151794 Hom.: 1 Cov.: 32 AF XY: 0.000809 AC XY: 60 AN XY: 74128

African (AFR) AF: 0.0000242 AC: 1 AN: 41348

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00855 AC: 41 AN: 4796

European-Finnish (FIN) AF: 0.0000957 AC: 1 AN: 10454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 67992

Other (OTH) AF: 0.000951 AC: 2 AN: 2102

Alfa AF: 0.000715 Hom.: 1

Bravo AF: 0.000378

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UGP2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.8
DANN	Benign	0.72
PhyloP100		-0.23
PromoterAI		-0.065	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs146746356; hg19: chr2-64069334;