Variant chr9-69174240-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201629.3(TJP2):c.-133C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,501,928 control chromosomes in the GnomAD database, including 143,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14110 hom., cov: 33)

Exomes 𝑓: 0.43 ( 128993 hom. )

Consequence

TJP2
NM_201629.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.506

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 9-69174240-C-T is Benign according to our data. Variant chr9-69174240-C-T is described in ClinVar as [Benign]. Clinvar id is 1277563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4 linkuse as main transcript			upstream_gene_variant		ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 linkuse as main transcript			upstream_gene_variant		1	NM_004817.4	ENSP00000366453	P2	Q9UDY2-1

Frequencies

GnomAD3 genomes

AF:

0.426

AC:

64721

AN:

151880

Hom.:

14086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.627

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.455

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.460

GnomAD4 exome

AF:

0.432

AC:

583534

AN:

1349936

Hom.:

128993

Cov.:

AF XY:

0.431

AC XY:

283922

AN XY:

658858

show subpopulations

Gnomad4 AFR exome

AF:

0.343

Gnomad4 AMR exome

AF:

0.653

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.658

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.420

Gnomad4 OTH exome

AF:

0.443

GnomAD4 genome

AF:

0.426

AC:

64777

AN:

151992

Hom.:

14110

Cov.:

AF XY:

0.430

AC XY:

31911

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.547

Gnomad4 ASJ

AF:

0.488

Gnomad4 EAS

AF:

0.627

Gnomad4 SAS

AF:

0.387

Gnomad4 FIN

AF:

0.469

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.426

Hom.:

1735

Bravo

AF:

0.433

Asia WGS

AF:

0.535

AC:

1853

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.2

Splicing

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