2-63882550-AAT-TCC

Variant names:

• chr2-63882550-AAT-TCC
• NM_006759.4:c.340_342delAATinsTCC
• UGP2 p.Asn114Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_006759.4(UGP2):​c.340_342delAATinsTCC​(p.Asn114Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGP2 NM_006759.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.27
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.340_342delAATinsTCC	p.Asn114Ser	missense	N/A	NP_006750.3
	UGP2	NM_001001521.2		c.307_309delAATinsTCC	p.Asn103Ser	missense	N/A	NP_001001521.1	Q16851-2
	UGP2	NM_001377524.1		c.307_309delAATinsTCC	p.Asn103Ser	missense	N/A	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.340_342delAATinsTCC	p.Asn114Ser	missense	N/A	ENSP00000338703.5	Q16851-1
	UGP2	ENST00000394417.7	TSL:1	c.307_309delAATinsTCC	p.Asn103Ser	missense	N/A	ENSP00000377939.2	Q16851-2
	UGP2	ENST00000467648.6	TSL:1	c.307_309delAATinsTCC	p.Asn103Ser	missense	N/A	ENSP00000420793.2	Q16851-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-64109684;