dbSNP rs11368509: UPP2:c.-25_-24insA (chr2-158102039-G-GA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001135098.2(UPP2):c.148-1_148insA(p.Val50fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 1,610,214 control chromosomes in the GnomAD database, including 4,457 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.10 ( 1596 hom., cov: 31)

Exomes 𝑓: 0.039 ( 2861 hom. )

Consequence

UPP2
NM_001135098.2 frameshift, splice_region

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.801

Publications

6 publications found

Variant links:

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]

UPP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135098.2. 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.-25_-24insA		5_prime_UTR	Exon 1 of 7	NP_775491.1
	UPP2	NM_001135098.2		c.148-1_148insA	p.Val50fs	frameshift splice_region	Exon 3 of 9	NP_001128570.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UPP2	ENST00000005756.5	TSL:1 MANE Select	c.-25_-24insA		5_prime_UTR	Exon 1 of 7	ENSP00000005756.5
UPP2	ENST00000605860.5	TSL:5	c.148-1_148insA	p.Val50fs	frameshift splice_region	Exon 4 of 10	ENSP00000474090.1
UPP2	ENST00000890005.1		c.-24-1_-24insA		splice_region	Exon 2 of 8	ENSP00000560064.1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15637

AN:

152012

Hom.:

1578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0570

Gnomad ASJ

AF:

0.0781

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0212

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0278

Gnomad OTH

AF:

0.0953

GnomAD2 exomes

AF:

0.0632

AC:

15755

AN:

249272

AF XY:

0.0616

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.0289

Gnomad ASJ exome

AF:

0.0726

Gnomad EAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.0188

Gnomad NFE exome

AF:

0.0300

Gnomad OTH exome

AF:

0.0489

GnomAD4 exome

AF:

0.0386

AC:

56351

AN:

1458084

Hom.:

2861

Cov.:

AF XY:

0.0401

AC XY:

29081

AN XY:

725346

show subpopulations

African (AFR)

AF:

0.277

AC:

9141

AN:

33048

American (AMR)

AF:

0.0333

AC:

1482

AN:

44460

Ashkenazi Jewish (ASJ)

AF:

0.0697

AC:

1814

AN:

26038

East Asian (EAS)

AF:

0.118

AC:

4676

AN:

39522

South Asian (SAS)

AF:

0.104

AC:

8909

AN:

85508

European-Finnish (FIN)

AF:

0.0195

AC:

1039

AN:

53268

Middle Eastern (MID)

AF:

0.110

AC:

631

AN:

5732

European-Non Finnish (NFE)

AF:

0.0227

AC:

25207

AN:

1110302

Other (OTH)

AF:

0.0573

AC:

3452

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

2329

4658

6988

9317

11646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1136

2272

3408

4544

5680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.103

AC:

15700

AN:

152130

Hom.:

1596

Cov.:

AF XY:

0.103

AC XY:

7626

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.263

AC:

10905

AN:

41446

American (AMR)

AF:

0.0569

AC:

870

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0781

AC:

271

AN:

3470

East Asian (EAS)

AF:

0.142

AC:

733

AN:

5166

South Asian (SAS)

AF:

0.110

AC:

533

AN:

4828

European-Finnish (FIN)

AF:

0.0212

AC:

225

AN:

10596

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0278

AC:

1888

AN:

68012

Other (OTH)

AF:

0.0967

AC:

204

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

632

1263

1895

2526

3158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0457

Hom.:

246

Bravo

AF:

0.113

Asia WGS

AF:

0.143

AC:

497

AN:

3478

EpiCase

AF:

0.0335

EpiControl

AF:

0.0355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.80

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over