2-158121282-A-G

Position:

• chr2-158121282-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.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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPP2	NM_173355.4	c.455-127A>G		intron_variant		ENST00000005756.5
UPP2	NM_001135098.2	c.626-127A>G		intron_variant
UPP2	XM_017003484.2	c.455-127A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPP2	ENST00000005756.5	c.455-127A>G		intron_variant		1	NM_173355.4	P1
UPP2	ENST00000605860.5	c.626-127A>G		intron_variant		5
UPP2	ENST00000460456.1	n.377-2467A>G		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.240

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.145

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

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.267

Gnomad4 SAS AF: 0.0979

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.164

Alfa AF: 0.131 Hom.: 3265

Bravo AF: 0.179

Asia WGS AF: 0.189 AC: 655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.2
DANN	Benign	0.80

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: rs2074955; hg19: chr2-158977794;