rs6709528

Variant names:

• chr2-158113913-C-T
• rs6709528
• NM_173355.4:c.181-1188C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UPP2	NM_173355.4	c.181-1188C>T		intron_variant	Intron 2 of 6	ENST00000005756.5	NP_775491.1
UPP2	NM_001135098.2	c.352-1188C>T		intron_variant	Intron 4 of 8		NP_001128570.1
UPP2	XM_017003484.2	c.181-1188C>T		intron_variant	Intron 2 of 5		XP_016858973.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPP2	ENST00000005756.5	c.181-1188C>T		intron_variant	Intron 2 of 6	1	NM_173355.4	ENSP00000005756.5

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

African (AFR) AF: 0.275 AC: 11426 AN: 41478

American (AMR) AF: 0.465 AC: 7100 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3470

East Asian (EAS) AF: 0.0551 AC: 285 AN: 5174

South Asian (SAS) AF: 0.326 AC: 1568 AN: 4814

European-Finnish (FIN) AF: 0.534 AC: 5643 AN: 10576

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34356 AN: 67968

Other (OTH) AF: 0.443 AC: 936 AN: 2114

Alfa AF: 0.447 Hom.: 2029

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
PhyloP100		-0.28
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: rs6709528; hg19: chr2-158970425;