rs202242009

Variant names:

• chr2-63885863-A-G
• rs202242009
• NM_006759.4:c.850A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006759.4(UGP2):​c.850A>G​(p.Asn284Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000062 in 1,596,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: UGP2 NM_006759.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39
• Publications: 3 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024383992).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGP2	NM_006759.4	MANE Select	c.850A>G	p.Asn284Asp	missense	Exon 6 of 10	NP_006750.3
	UGP2	NM_001001521.2		c.817A>G	p.Asn273Asp	missense	Exon 6 of 10	NP_001001521.1	Q16851-2
	UGP2	NM_001377524.1		c.817A>G	p.Asn273Asp	missense	Exon 7 of 11	NP_001364453.1	A0A140VKE1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGP2	ENST00000337130.10	TSL:1 MANE Select	c.850A>G	p.Asn284Asp	missense	Exon 6 of 10	ENSP00000338703.5	Q16851-1
	UGP2	ENST00000394417.7	TSL:1	c.817A>G	p.Asn273Asp	missense	Exon 6 of 10	ENSP00000377939.2	Q16851-2
	UGP2	ENST00000467648.6	TSL:1	c.817A>G	p.Asn273Asp	missense	Exon 7 of 11	ENSP00000420793.2	Q16851-2

Frequencies

GnomAD3 genomes AF: 0.000315 AC: 48 AN: 152250 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000955

GnomAD2 exomes AF: 0.0000940 AC: 22 AN: 234166 AF XY: 0.0000630

Gnomad AFR exome AF: 0.00122

Gnomad AMR exome AF: 0.0000974

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000353 AC: 51 AN: 1444186 Hom.: 0 Cov.: 33 AF XY: 0.0000306 AC XY: 22 AN XY: 717984

African (AFR) AF: 0.00141 AC: 46 AN: 32558

American (AMR) AF: 0.0000487 AC: 2 AN: 41060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25218

East Asian (EAS) AF: 0.00 AC: 0 AN: 39196

South Asian (SAS) AF: 0.00 AC: 0 AN: 83378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104616

Other (OTH) AF: 0.0000504 AC: 3 AN: 59550

GnomAD4 genome AF: 0.000315 AC: 48 AN: 152368 Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74518

African (AFR) AF: 0.00108 AC: 45 AN: 41590

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.0000652 Hom.: 0

Bravo AF: 0.000397

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	20
DANN	Benign	0.81
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-2.1	N
PhyloP100		5.4
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	3.8	N
REVEL	Benign	0.084
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.21
MVP		0.13
MPC		0.58
ClinPred		0.049	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.84
Mutation Taster		=54/46	polymorphism

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: rs202242009; hg19: chr2-64112997; COSMIC: COSV61427475; COSMIC: COSV61427475;