rs72709079

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004817.4(TJP2):c.297G>A(p.Ser99Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,614,138 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 11 hom., cov: 32)

Exomes 𝑓: 0.015 ( 187 hom. )

Consequence

TJP2
NM_004817.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.951

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 9-69218314-G-A is Benign according to our data. Variant chr9-69218314-G-A is described in ClinVar as [Benign]. Clinvar id is 44097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.951 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0147 (21548/1461846) while in subpopulation NFE AF= 0.0174 (19323/1111974). AF 95% confidence interval is 0.0172. There are 187 homozygotes in gnomad4_exome. There are 10571 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4 link	c.297G>A	p.Ser99Ser	synonymous_variant	Exon 4 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.297G>A	p.Ser99Ser	synonymous_variant	Exon 4 of 23	1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 link	c.684G>A	p.Ser228Ser	synonymous_variant	Exon 6 of 25			ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.00940

AC:

1430

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0157

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00990

AC:

2490

AN:

251486

Hom.:

AF XY:

0.00977

AC XY:

1328

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00474

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00441

Gnomad FIN exome

AF:

0.0117

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.00993

GnomAD4 exome

AF:

0.0147

AC:

21548

AN:

1461846

Hom.:

187

Cov.:

AF XY:

0.0145

AC XY:

10571

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00496

Gnomad4 ASJ exome

AF:

0.00647

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00442

Gnomad4 FIN exome

AF:

0.0112

Gnomad4 NFE exome

AF:

0.0174

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.00939

AC:

1430

AN:

152292

Hom.:

Cov.:

AF XY:

0.00896

AC XY:

667

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.0157

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0136

Hom.:

Bravo

AF:

0.00891

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 29, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ser76Ser in Exon 05 of TJP2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1.6% (115/7020) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs72709079). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.83

DANN

Benign

0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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