2-158121282-A-G

Variant names:

• chr2-158121282-A-G
• rs2074955
• NM_173355.4:c.455-127A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173355.4(UPP2):​c.455-127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 827,360 control chromosomes in the GnomAD database, including 9,371 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 0.17 (2711 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6660 hom.)
• Consequence: UPP2 NM_173355.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173355.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPP2	NM_173355.4	MANE Select	c.455-127A>G		intron	N/A	NP_775491.1	A0A0S2Z634
	UPP2	NM_001135098.2		c.626-127A>G		intron	N/A	NP_001128570.1	O95045-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPP2	ENST00000005756.5	TSL:1 MANE Select	c.455-127A>G		intron	N/A	ENSP00000005756.5	O95045-1
	UPP2	ENST00000605860.5	TSL:5	c.626-127A>G		intron	N/A	ENSP00000474090.1	O95045-2
	UPP2	ENST00000890005.1		c.455-127A>G		intron	N/A	ENSP00000560064.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25870 AN: 151806 Hom.: 2706 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.163

GnomAD4 exome AF: 0.130 AC: 87612 AN: 675436 Hom.: 6660 AF XY: 0.128 AC XY: 45088 AN XY: 352890

African (AFR) AF: 0.280 AC: 4768 AN: 17056

American (AMR) AF: 0.133 AC: 3723 AN: 27922

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 2177 AN: 15994

East Asian (EAS) AF: 0.240 AC: 8527 AN: 35600

South Asian (SAS) AF: 0.0912 AC: 4969 AN: 54458

European-Finnish (FIN) AF: 0.109 AC: 5324 AN: 49036

Middle Eastern (MID) AF: 0.134 AC: 405 AN: 3018

European-Non Finnish (NFE) AF: 0.120 AC: 52878 AN: 438950

Other (OTH) AF: 0.145 AC: 4841 AN: 33402

GnomAD4 genome AF: 0.171 AC: 25905 AN: 151924 Hom.: 2711 Cov.: 32 AF XY: 0.166 AC XY: 12367 AN XY: 74286

African (AFR) AF: 0.279 AC: 11553 AN: 41456

American (AMR) AF: 0.136 AC: 2078 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 428 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1381 AN: 5170

South Asian (SAS) AF: 0.0979 AC: 472 AN: 4820

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10586

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.124 AC: 8442 AN: 67874

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.142 Hom.: 6076

Bravo AF: 0.179

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.80
PhyloP100		0.23
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: rs2074955; hg19: chr2-158977794;