Variant 9-69237989-T-G 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_004817.4(TJP2):c.2275+16T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,566,400 control chromosomes in the GnomAD database, including 645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 333 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 312 hom. )

Consequence

TJP2
NM_004817.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.709

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 9-69237989-T-G is Benign according to our data. Variant chr9-69237989-T-G is described in ClinVar as [Benign]. Clinvar id is 259552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 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	c.2275+16T>G		intron_variant		ENST00000377245.9	NP_004808.2	Q9UDY2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9 linkuse as main transcript	c.2275+16T>G		intron_variant		1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 linkuse as main transcript	c.2662+16T>G		intron_variant				ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.0379

AC:

5736

AN:

151308

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00661

Gnomad AMR

AF:

0.0238

Gnomad ASJ

AF:

0.00635

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000627

Gnomad FIN

AF:

0.000381

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00192

Gnomad OTH

AF:

0.0376

GnomAD3 exomes

AF:

0.0121

AC:

2914

AN:

240798

Hom.:

137

AF XY:

0.00951

AC XY:

1237

AN XY:

130022

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.00598

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000510

Gnomad FIN exome

AF:

0.000820

Gnomad NFE exome

AF:

0.00240

Gnomad OTH exome

AF:

0.0128

GnomAD4 exome

AF:

0.00534

AC:

7560

AN:

1414980

Hom.:

312

Cov.:

AF XY:

0.00475

AC XY:

3351

AN XY:

706152

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.0149

Gnomad4 ASJ exome

AF:

0.00484

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000588

Gnomad4 FIN exome

AF:

0.000819

Gnomad4 NFE exome

AF:

0.00147

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0379

AC:

5746

AN:

151420

Hom.:

333

Cov.:

AF XY:

0.0365

AC XY:

2704

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0238

Gnomad4 ASJ

AF:

0.00635

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000418

Gnomad4 FIN

AF:

0.000381

Gnomad4 NFE

AF:

0.00192

Gnomad4 OTH

AF:

0.0372

Alfa

AF:

0.0252

Hom.:

Bravo

AF:

0.0442

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.26

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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