9-69226102-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004817.4(TJP2):c.1137A>G(p.Leu379Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,614,094 control chromosomes in the GnomAD database, including 4,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 653 hom., cov: 33)

Exomes 𝑓: 0.065 ( 3371 hom. )

Consequence

TJP2
NM_004817.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.58

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]

TJP2 links:

ENSG00000285130 (HGNC:):

ENSG00000285130 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 9-69226102-A-G is Benign according to our data. Variant chr9-69226102-A-G is described in ClinVar as [Benign]. Clinvar id is 44090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.58 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4 link	c.1137A>G	p.Leu379Leu	synonymous_variant	Exon 7 of 23	ENST00000377245.9	NP_004808.2	Q9UDY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 link	c.1137A>G	p.Leu379Leu	synonymous_variant	Exon 7 of 23	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 link	c.1524A>G	p.Leu508Leu	synonymous_variant	Exon 9 of 25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.0837

AC:

12729

AN:

152162

Hom.:

652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0948

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.0982

Gnomad SAS

AF:

0.0839

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0563

Gnomad OTH

AF:

0.0865

GnomAD3 exomes

AF:

0.0683

AC:

17182

AN:

251394

Hom.:

688

AF XY:

0.0673

AC XY:

9149

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.0786

Gnomad ASJ exome

AF:

0.0521

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.0816

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0557

Gnomad OTH exome

AF:

0.0688

GnomAD4 exome

AF:

0.0647

AC:

94547

AN:

1461814

Hom.:

3371

Cov.:

AF XY:

0.0647

AC XY:

47021

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.0808

Gnomad4 ASJ exome

AF:

0.0515

Gnomad4 EAS exome

AF:

0.0864

Gnomad4 SAS exome

AF:

0.0812

Gnomad4 FIN exome

AF:

0.0210

Gnomad4 NFE exome

AF:

0.0615

Gnomad4 OTH exome

AF:

0.0709

GnomAD4 genome

AF:

0.0837

AC:

12743

AN:

152280

Hom.:

653

Cov.:

AF XY:

0.0825

AC XY:

6143

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0947

Gnomad4 ASJ

AF:

0.0458

Gnomad4 EAS

AF:

0.0983

Gnomad4 SAS

AF:

0.0835

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.0563

Gnomad4 OTH

AF:

0.0880

Alfa

AF:

0.0666

Hom.:

463

Bravo

AF:

0.0934

Asia WGS

AF:

0.100

AC:

348

AN:

3478

EpiCase

AF:

0.0592

EpiControl

AF:

0.0610

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Leu356Leu in Exon 08 of TJP2: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 14.1% (528/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs17062695). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

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

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.45

DANN

Benign

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over