2-158115173-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173355.4(UPP2):c.253G>C(p.Glu85Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UPP2 NM_173355.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.593

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1065388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UPP2	NM_173355.4	c.253G>C	p.Glu85Gln	missense_variant	3/7	ENST00000005756.5
UPP2	NM_001135098.2	c.424G>C	p.Glu142Gln	missense_variant	5/9
UPP2	XM_017003484.2	c.253G>C	p.Glu85Gln	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UPP2	ENST00000005756.5	c.253G>C	p.Glu85Gln	missense_variant	3/7	1	NM_173355.4	P1
UPP2	ENST00000605860.5	c.424G>C	p.Glu142Gln	missense_variant	6/10	5
UPP2	ENST00000460456.1	n.377-8576G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.424G>C (p.E142Q) alteration is located in exon 5 (coding exon 5) of the UPP2 gene. This alteration results from a G to C substitution at nucleotide position 424, causing the glutamic acid (E) at amino acid position 142 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	7.7
Dann	Benign	0.72
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
Sift4G	Benign	0.32	T;T
Polyphen		0.16	.;B
Vest4		0.15
MutPred		0.35		.;Loss of disorder (P = 0.0898);
MVP		0.81
MPC		0.17
ClinPred		0.063	T
GERP RS		0.86
Varity_R		0.23
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-158971685; COSMIC: COSV99134990;