2-63885572-CTTT-CTTTTT

Variant names:

• chr2-63885572-C-CTT
• rs751800377
• NM_006759.4:c.576-6_576-5dupTT

Variant summary

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

The NM_006759.4(UGP2):​c.576-6_576-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000659 in 955,612 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: UGP2 NM_006759.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• 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 0 ACMG points.

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.576-6_576-5dupTT		splice_region intron	N/A	NP_006750.3
	UGP2	NM_001001521.2		c.543-6_543-5dupTT		splice_region intron	N/A	NP_001001521.1	Q16851-2
	UGP2	NM_001377524.1		c.543-6_543-5dupTT		splice_region intron	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.576-17_576-16insTT		intron	N/A	ENSP00000338703.5	Q16851-1
	UGP2	ENST00000394417.7	TSL:1	c.543-17_543-16insTT		intron	N/A	ENSP00000377939.2	Q16851-2
	UGP2	ENST00000467648.6	TSL:1	c.543-17_543-16insTT		intron	N/A	ENSP00000420793.2	Q16851-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000177 AC: 15 AN: 84626 AF XY: 0.000176

Gnomad AFR exome AF: 0.000296

Gnomad AMR exome AF: 0.000123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000624

Gnomad FIN exome AF: 0.000127

Gnomad NFE exome AF: 0.000111

Gnomad OTH exome AF: 0.000571

GnomAD4 exome AF: 0.0000659 AC: 63 AN: 955612 Hom.: 0 Cov.: 18 AF XY: 0.0000865 AC XY: 41 AN XY: 473932

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000143 AC: 3 AN: 21006

American (AMR) AF: 0.0000993 AC: 2 AN: 20144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14922

East Asian (EAS) AF: 0.000109 AC: 3 AN: 27436

South Asian (SAS) AF: 0.000256 AC: 13 AN: 50868

European-Finnish (FIN) AF: 0.0000544 AC: 2 AN: 36744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4212

European-Non Finnish (NFE) AF: 0.0000513 AC: 38 AN: 741060

Other (OTH) AF: 0.0000510 AC: 2 AN: 39220

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.000149 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

Splicing

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

Other links and lift over

dbSNP: rs751800377; hg19: chr2-64112706;