2-63857980-G-A

Variant names:

• chr2-63857980-G-A
• rs10183479
• NM_006759.4:c.255+44G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006759.4(UGP2):​c.255+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 1,582,402 control chromosomes in the GnomAD database, including 533,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (52337 hom., cov: 31)
  • Exomes 𝑓: 0.82 (480772 hom.)
• Consequence: UGP2 NM_006759.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0370
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-63857980-G-A is Benign according to our data. Variant chr2-63857980-G-A is described in ClinVar as [Benign]. Clinvar id is 1684237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGP2	NM_006759.4	c.255+44G>A		intron_variant	Intron 3 of 9	ENST00000337130.10	NP_006750.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGP2	ENST00000337130.10	c.255+44G>A		intron_variant	Intron 3 of 9	1	NM_006759.4	ENSP00000338703.5

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125901 AN: 151984 Hom.: 52275 Cov.: 31

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.910

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.821

GnomAD2 exomes AF: 0.830 AC: 205051 AN: 246984 AF XY: 0.827

Gnomad AFR exome AF: 0.834

Gnomad AMR exome AF: 0.846

Gnomad ASJ exome AF: 0.766

Gnomad EAS exome AF: 0.912

Gnomad FIN exome AF: 0.880

Gnomad NFE exome AF: 0.813

Gnomad OTH exome AF: 0.812

GnomAD4 exome AF: 0.819 AC: 1171731 AN: 1430300 Hom.: 480772 Cov.: 22 AF XY: 0.818 AC XY: 583314 AN XY: 713324

African (AFR) AF: 0.837 AC: 27147 AN: 32448

American (AMR) AF: 0.842 AC: 36908 AN: 43812

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 19611 AN: 25680

East Asian (EAS) AF: 0.926 AC: 36526 AN: 39430

South Asian (SAS) AF: 0.812 AC: 69060 AN: 85050

European-Finnish (FIN) AF: 0.881 AC: 46717 AN: 53016

Middle Eastern (MID) AF: 0.750 AC: 4255 AN: 5674

European-Non Finnish (NFE) AF: 0.813 AC: 882870 AN: 1086026

Other (OTH) AF: 0.822 AC: 48637 AN: 59164

GnomAD4 genome AF: 0.829 AC: 126022 AN: 152102 Hom.: 52337 Cov.: 31 AF XY: 0.830 AC XY: 61741 AN XY: 74356

African (AFR) AF: 0.838 AC: 34769 AN: 41492

American (AMR) AF: 0.832 AC: 12710 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2712 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4724 AN: 5166

South Asian (SAS) AF: 0.815 AC: 3923 AN: 4816

European-Finnish (FIN) AF: 0.876 AC: 9261 AN: 10566

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.811 AC: 55122 AN: 67998

Other (OTH) AF: 0.824 AC: 1739 AN: 2110

Alfa AF: 0.796 Hom.: 7000

Bravo AF: 0.827

Asia WGS AF: 0.893 AC: 3104 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 83 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		0.037
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: rs10183479; hg19: chr2-64085114;