rs6437133

Positions:

• chr2-158107775-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173355.4(UPP2):​c.180+1559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,934 control chromosomes in the GnomAD database, including 23,057 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23057 hom., cov: 31)
• Consequence: UPP2 NM_173355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPP2	NM_173355.4	c.180+1559A>G		intron_variant		ENST00000005756.5
UPP2	NM_001135098.2	c.351+1559A>G		intron_variant
UPP2	XM_017003484.2	c.180+1559A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPP2	ENST00000005756.5	c.180+1559A>G		intron_variant		1	NM_173355.4	P1
UPP2	ENST00000605860.5	c.351+1559A>G		intron_variant		5
UPP2	ENST00000460456.1	n.376+1559A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.540 AC: 81985 AN: 151816 Hom.: 23043 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.0567

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.540 AC: 82044 AN: 151934 Hom.: 23057 Cov.: 31 AF XY: 0.534 AC XY: 39643 AN XY: 74236

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.495

Gnomad4 EAS AF: 0.0564

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.565

Alfa AF: 0.536 Hom.: 9704

Bravo AF: 0.545

Asia WGS AF: 0.291 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.58

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: rs6437133; hg19: chr2-158964287;