11-118957207-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM2PP3BP6_Very_Strong

The NM_006760.4(UPK2):​c.209-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

UPK2
NM_006760.4 splice_acceptor, intron

Scores

2
3
2
Splicing: ADA: 1.000
2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, MutationTaster, phyloP100way_vertebrate was below the threshold]
BP6
Variant 11-118957207-G-A is Benign according to our data. Variant chr11-118957207-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 743363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UPK2NM_006760.4 linkc.209-1G>A splice_acceptor_variant, intron_variant Intron 2 of 4 ENST00000264031.3 NP_006751.1 O00526

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UPK2ENST00000264031.3 linkc.209-1G>A splice_acceptor_variant, intron_variant Intron 2 of 4 1 NM_006760.4 ENSP00000264031.2 O00526
UPK2ENST00000534788.1 linkn.323-1G>A splice_acceptor_variant, intron_variant Intron 3 of 5 3

Frequencies

GnomAD3 genomes
AF:
0.000821
AC:
125
AN:
152166
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00294
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000175
AC:
44
AN:
251288
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135796
show subpopulations
Gnomad AFR exome
AF:
0.00252
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000746
AC:
109
AN:
1461786
Hom.:
0
Cov.:
33
AF XY:
0.0000564
AC XY:
41
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00263
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000821
AC:
125
AN:
152284
Hom.:
0
Cov.:
31
AF XY:
0.000739
AC XY:
55
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00294
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000119
Hom.:
0
Bravo
AF:
0.000903
ESP6500AA
AF:
0.00205
AC:
9
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000206
AC:
25
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jun 20, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
30
DANN
Uncertain
0.99
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.85
D
GERP RS
5.8

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.94
SpliceAI score (max)
0.61
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.32
Position offset: 14
DS_AL_spliceai
0.61
Position offset: 1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77809657; hg19: chr11-118827917; COSMIC: COSV50629166; API