dbSNP rs141565726: UPK2:p.Gly93Asp (chr11-118957277-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006760.4(UPK2):c.278G>A(p.Gly93Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,160 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 28 hom. )

Consequence

UPK2
NM_006760.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.33

Publications

7 publications found

Variant links:

Genes affected

UPK2 (HGNC:12579): (uroplakin 2) This gene encodes one of the proteins of the highly conserved urothelium-specific integral membrane proteins of the asymmetric unit membrane which forms urothelium apical plaques in mammals. The asymmetric unit membrane is believed to strengthen the urothelium by preventing cell rupture during bladder distention. The encoded protein is expressed in the peripheral blood of bladder cancer patients with transitional cell carcinomas.[provided by RefSeq, Sep 2009]

UPK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069190264).

BP6

Variant 11-118957277-G-A is Benign according to our data. Variant chr11-118957277-G-A is described in ClinVar as Benign. ClinVar VariationId is 784218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00186 (2713/1461880) while in subpopulation AMR AF = 0.0309 (1380/44724). AF 95% confidence interval is 0.0295. There are 28 homozygotes in GnomAdExome4. There are 1240 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006760.4. 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
	UPK2	NM_006760.4	MANE Select	c.278G>A	p.Gly93Asp	missense	Exon 3 of 5	NP_006751.1	O00526

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPK2	ENST00000264031.3	TSL:1 MANE Select	c.278G>A	p.Gly93Asp	missense	Exon 3 of 5	ENSP00000264031.2	O00526
	UPK2	ENST00000534788.1	TSL:3	n.392G>A		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

474

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0145

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00652

AC:

1640

AN:

251428

AF XY:

0.00536

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.0337

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00794

Gnomad FIN exome

AF:

0.00947

Gnomad NFE exome

AF:

0.000651

Gnomad OTH exome

AF:

0.00391

GnomAD4 exome

AF:

0.00186

AC:

2713

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1240

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33480

American (AMR)

AF:

0.0309

AC:

1380

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00889

AC:

353

AN:

39700

South Asian (SAS)

AF:

0.000684

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00833

AC:

445

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000298

AC:

331

AN:

1112008

Other (OTH)

AF:

0.00215

AC:

130

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

161

322

484

645

806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.00311

AC:

474

AN:

152280

Hom.:

Cov.:

AF XY:

0.00369

AC XY:

275

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41548

American (AMR)

AF:

0.0145

AC:

222

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00849

AC:

AN:

5182

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0103

AC:

109

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000764

AC:

AN:

68026

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00193

Hom.:

Bravo

AF:

0.00383

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.00530

AC:

643

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.90

MutationAssessor

Benign

2.0

PhyloP100

3.3

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.32

Sift

Benign

0.26

Sift4G

Benign

0.36

Polyphen

0.98

Vest4

0.54

MVP

0.51

MPC

0.61

ClinPred

0.028

GERP RS

6.0

Varity_R

0.39

gMVP

0.48

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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