rs199852211

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_004817.4(TJP2):​c.2819C>T​(p.Pro940Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000199 in 1,613,240 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

TJP2
NM_004817.4 missense

Scores

4
15

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.04
Variant links:
Genes affected
TJP2 (HGNC:11828): (tight junction protein 2) This gene encodes a zonula occluden that is a member of the membrane-associated guanylate kinase homolog family. The encoded protein functions as a component of the tight junction barrier in epithelial and endothelial cells and is necessary for proper assembly of tight junctions. Mutations in this gene have been identified in patients with hypercholanemia, and genomic duplication of a 270 kb region including this gene causes autosomal dominant deafness-51. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0053499043).
BP6
Variant 9-69248163-C-T is Benign according to our data. Variant chr9-69248163-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 228009.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
TJP2NM_004817.4 linkc.2819C>T p.Pro940Leu missense_variant Exon 19 of 23 ENST00000377245.9 NP_004808.2 Q9UDY2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TJP2ENST00000377245.9 linkc.2819C>T p.Pro940Leu missense_variant Exon 19 of 23 1 NM_004817.4 ENSP00000366453.4 Q9UDY2-1
ENSG00000285130ENST00000642889.1 linkc.3206C>T p.Pro1069Leu missense_variant Exon 21 of 25 ENSP00000493780.1 A0A2R8YDH4

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000375
AC:
93
AN:
247682
Hom.:
1
AF XY:
0.000476
AC XY:
64
AN XY:
134386
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000552
Gnomad SAS exome
AF:
0.00295
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000898
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.000208
AC:
304
AN:
1460912
Hom.:
1
Cov.:
32
AF XY:
0.000310
AC XY:
225
AN XY:
726756
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00328
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.000299
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152328
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00352
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.000512
AC:
62
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
May 12, 2015
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

p.Pro940Leu in exon 19 of TJP2: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (60/15540) of South Asian chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs199852211). -

TJP2-related disorder Benign:1
Sep 18, 2023
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1
Nov 21, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
.;.;.;T;.;T;.;.;.;.;.;.;.
Eigen
Benign
-0.060
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.85
T;T;D;.;T;D;T;T;T;T;T;D;D
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.0053
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.94
.;.;.;L;L;L;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.4
.;N;.;.;N;D;.;.;.;D;.;D;.
REVEL
Benign
0.042
Sift
Benign
0.30
.;T;.;.;T;T;.;.;.;T;.;T;.
Sift4G
Benign
0.27
.;T;.;.;T;T;.;.;.;T;.;T;.
Polyphen
0.0090, 0.0050
.;.;.;B;B;B;.;.;.;.;.;.;.
Vest4
0.27, 0.28, 0.25, 0.32, 0.33
MutPred
0.23
.;.;.;Loss of glycosylation at P940 (P = 0.1832);Loss of glycosylation at P940 (P = 0.1832);Loss of glycosylation at P940 (P = 0.1832);Loss of glycosylation at P940 (P = 0.1832);Loss of glycosylation at P940 (P = 0.1832);.;.;.;.;.;
MVP
0.59
MPC
0.26
ClinPred
0.059
T
GERP RS
5.2
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.1
Varity_R
0.061
gMVP
0.25

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

LitVar

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

Other links and lift over

dbSNP: rs199852211; hg19: chr9-71863079; API