rs6709528

chr2-158113913-C-T

Variant summary

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

The NM_173355.4(UPP2):c.181-1188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,082 control chromosomes in the GnomAD database, including 14,425 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 0.42 (14425 hom., cov: 32)
• Consequence: UPP2 NM_173355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPP2	NM_173355.4	c.181-1188C>T		intron_variant		ENST00000005756.5
UPP2	NM_001135098.2	c.352-1188C>T		intron_variant
UPP2	XM_017003484.2	c.181-1188C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPP2	ENST00000005756.5	c.181-1188C>T		intron_variant		1	NM_173355.4	P1
UPP2	ENST00000605860.5	c.352-1188C>T		intron_variant		5
UPP2	ENST00000460456.1	n.376+7697C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63528 AN: 151964 Hom.: 14434 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.418 AC: 63518 AN: 152082 Hom.: 14425 Cov.: 32 AF XY: 0.416 AC XY: 30910 AN XY: 74328

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.0551

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.443

Alfa AF: 0.453 Hom.: 1999

Bravo AF: 0.408

Asia WGS AF: 0.217 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.4
Dann	Benign	0.68

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: rs6709528; hg19: chr2-158970425;