rs4404222

Positions:

• chr2-157886996-G-A
• chr2-157886996-G-C

Variant summary

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

The ENST00000605860.5(UPP2):​c.-20+10268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 147,408 control chromosomes in the GnomAD database, including 2,166 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 0.14 (2166 hom., cov: 27)
• Consequence: UPP2 ENST00000605860.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578

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]

LOC105373714 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105373714	XR_923517.3	n.145+10268G>A		intron_variant
LOC105373714	XR_923518.3	n.133+10280G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPP2	ENST00000605860.5	c.-20+10268G>A		intron_variant		5		ENSP00000474090.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21086 AN: 147370 Hom.: 2165 Cov.: 27

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0921

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0839

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.143 AC: 21101 AN: 147408 Hom.: 2166 Cov.: 27 AF XY: 0.144 AC XY: 10338 AN XY: 71590

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.0921

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.134

Alfa AF: 0.106 Hom.: 638

Bravo AF: 0.153

Asia WGS AF: 0.278 AC: 961 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4404222; hg19: chr2-158743508;