2-63889455-G-A

Variant names:

• chr2-63889455-G-A
• rs6546038
• ENST00000475550.5:n.3224G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000475550.5(UGP2):​n.3224G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.77 in 152,036 control chromosomes in the GnomAD database, including 46,513 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (46485 hom., cov: 29)
  • Exomes 𝑓: 0.76 (28 hom.)
• Consequence: UGP2 ENST00000475550.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000475550.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGP2	NM_006759.4	MANE Select	c.1315-626G>A		intron	N/A	NP_006750.3
	UGP2	NM_001001521.2		c.1282-626G>A		intron	N/A	NP_001001521.1
	UGP2	NM_001377524.1		c.1282-626G>A		intron	N/A	NP_001364453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGP2	ENST00000475550.5	TSL:1	n.3224G>A		non_coding_transcript_exon	Exon 6 of 7
	UGP2	ENST00000337130.10	TSL:1 MANE Select	c.1315-626G>A		intron	N/A	ENSP00000338703.5
	UGP2	ENST00000394417.7	TSL:1	c.1282-626G>A		intron	N/A	ENSP00000377939.2

Frequencies

GnomAD3 genomes AF: 0.770 AC: 116951 AN: 151824 Hom.: 46442 Cov.: 29

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.755 AC: 71 AN: 94 Hom.: 28 Cov.: 0 AF XY: 0.727 AC XY: 48 AN XY: 66

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.833 AC: 5 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.811 AC: 60 AN: 74

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.770 AC: 117052 AN: 151942 Hom.: 46485 Cov.: 29 AF XY: 0.765 AC XY: 56789 AN XY: 74242

African (AFR) AF: 0.888 AC: 36810 AN: 41454

American (AMR) AF: 0.691 AC: 10561 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2541 AN: 3466

East Asian (EAS) AF: 0.228 AC: 1173 AN: 5146

South Asian (SAS) AF: 0.579 AC: 2785 AN: 4810

European-Finnish (FIN) AF: 0.762 AC: 8011 AN: 10520

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52800 AN: 67952

Other (OTH) AF: 0.755 AC: 1594 AN: 2110

Alfa AF: 0.768 Hom.: 56144

Bravo AF: 0.767

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.73
DANN	Benign	0.79
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6546038; hg19: chr2-64116589;