rs199852211
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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
NM_004817.4 missense
Scores
3
10
Clinical Significance
Conservation
PhyloP100: 4.04
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]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.2819C>T | p.Pro940Leu | missense_variant | 19/23 | ENST00000377245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.2819C>T | p.Pro940Leu | missense_variant | 19/23 | 1 | NM_004817.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152210Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000375 AC: 93AN: 247682Hom.: 1 AF XY: 0.000476 AC XY: 64AN XY: 134386
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GnomAD4 exome AF: 0.000208 AC: 304AN: 1460912Hom.: 1 Cov.: 32 AF XY: 0.000310 AC XY: 225AN XY: 726756
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GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74482
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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
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 12, 2015 | 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
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 18, 2023 | 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;D;.;T;D;T;T;T;T;T;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
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
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at