NM_006759.4:c.576-5dupT

Variant names:

• chr2-63885572-C-CT
• rs751800377
• NM_006759.4:c.576-5dupT

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP6 BS1

The NM_006759.4(UGP2):​c.576-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0241 in 976,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.028 (0 hom.)
• Consequence: UGP2 NM_006759.4 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.249

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-63885572-C-CT is Benign according to our data. Variant chr2-63885572-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 3059622.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.028 (23298/830894) while in subpopulation SAS AF= 0.0484 (2275/47028). AF 95% confidence interval is 0.0467. There are 0 homozygotes in gnomad4_exome. There are 11674 alleles in male gnomad4_exome subpopulation. Median coverage is 18. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGP2	NM_006759.4	c.576-5dupT		splice_region_variant, intron_variant	Intron 5 of 9	ENST00000337130.10	NP_006750.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGP2	ENST00000337130.10	c.576-17_576-16insT		intron_variant	Intron 5 of 9	1	NM_006759.4	ENSP00000338703.5

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 248 AN: 145924 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00233

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000871

Gnomad FIN AF: 0.00173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000424

Gnomad OTH AF: 0.00101

GnomAD4 exome AF: 0.0280 AC: 23298 AN: 830894 Hom.: 0 Cov.: 18 AF XY: 0.0282 AC XY: 11674 AN XY: 413742

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.0258

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.0259

Gnomad4 SAS exome AF: 0.0484

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0263

Gnomad4 OTH exome AF: 0.0309

GnomAD4 genome AF: 0.00173 AC: 252 AN: 145998 Hom.: 0 Cov.: 32 AF XY: 0.00199 AC XY: 141 AN XY: 70934

Gnomad4 AFR AF: 0.00420

Gnomad4 AMR AF: 0.00233

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000874

Gnomad4 FIN AF: 0.00173

Gnomad4 NFE AF: 0.000424

Gnomad4 OTH AF: 0.00100

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

UGP2-related disorder Benign:1

Dec 14, 2020

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs751800377; hg19: chr2-64112706;