rs11368509

Positions:

• chr2-158102039-G-GA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001135098.2(UPP2):​c.148-1_148insA​(p.Val50fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 1,610,214 control chromosomes in the GnomAD database, including 4,457 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.10 (1596 hom., cov: 31)
  • Exomes 𝑓: 0.039 (2861 hom.)
• Consequence: UPP2 NM_001135098.2 frameshift, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801

Genes affected

UPP2 (HGNC:23061): (uridine phosphorylase 2) Enables deoxyuridine phosphorylase activity; identical protein binding activity; and uridine phosphorylase activity. Involved in dCMP catabolic process and uridine catabolic process. Located in type III intermediate filament. [provided by Alliance of Genome Resources, Apr 2022]

UPP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPP2	NM_173355.4	c.-25_-24insA		5_prime_UTR_variant	1/7	ENST00000005756.5	NP_775491.1
UPP2	NM_001135098.2	c.148-1_148insA	p.Val50fs	frameshift_variant, splice_region_variant	3/9		NP_001128570.1
UPP2	XM_017003484.2	c.-25_-24insA		5_prime_UTR_variant	1/6		XP_016858973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPP2	ENST00000005756	c.-25_-24insA		5_prime_UTR_variant	1/7	1	NM_173355.4	ENSP00000005756.5
UPP2	ENST00000605860.5	c.148-1_148insA	p.Val50fs	frameshift_variant, splice_region_variant	4/10	5		ENSP00000474090.1
UPP2	ENST00000460456.1	n.172_173insA		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15637 AN: 152012 Hom.: 1578 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0212

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0953

GnomAD3 exomes AF: 0.0632 AC: 15755 AN: 249272 Hom.: 1092 AF XY: 0.0616 AC XY: 8296 AN XY: 134724

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.0289

Gnomad ASJ exome AF: 0.0726

Gnomad EAS exome AF: 0.133

Gnomad SAS exome AF: 0.107

Gnomad FIN exome AF: 0.0188

Gnomad NFE exome AF: 0.0300

Gnomad OTH exome AF: 0.0489

GnomAD4 exome AF: 0.0386 AC: 56351 AN: 1458084 Hom.: 2861 Cov.: 31 AF XY: 0.0401 AC XY: 29081 AN XY: 725346

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0697

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0195

Gnomad4 NFE exome AF: 0.0227

Gnomad4 OTH exome AF: 0.0573

GnomAD4 genome AF: 0.103 AC: 15700 AN: 152130 Hom.: 1596 Cov.: 31 AF XY: 0.103 AC XY: 7626 AN XY: 74386

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0781

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0212

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0967

Alfa AF: 0.0457 Hom.: 246

Bravo AF: 0.113

Asia WGS AF: 0.143 AC: 497 AN: 3478

EpiCase AF: 0.0335

EpiControl AF: 0.0355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs11368509; hg19: chr2-158958551; COSMIC: COSV50046721;