Variant 9-69248319-A-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.2880+95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 1,484,356 control chromosomes in the GnomAD database, including 4,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 432 hom., cov: 32)

Exomes 𝑓: 0.079 ( 4367 hom. )

Consequence

TJP2
NM_004817.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.522

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=-0.81).

BP6

Variant 9-69248319-A-G is Benign according to our data. Variant chr9-69248319-A-G is described in ClinVar as [Benign]. Clinvar id is 44109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.081 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.2880+95A>G		intron_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	c.2880+95A>G		intron_variant		1	NM_004817.4	ENSP00000366453	P2	Q9UDY2-1

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

10824

AN:

152130

Hom.:

430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0559

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0600

Gnomad ASJ

AF:

0.0562

Gnomad EAS

AF:

0.00598

Gnomad SAS

AF:

0.0854

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0828

Gnomad OTH

AF:

0.0771

GnomAD3 exomes

AF:

0.0661

AC:

6723

AN:

101664

Hom.:

246

AF XY:

0.0687

AC XY:

3489

AN XY:

50806

show subpopulations

Gnomad AFR exome

AF:

0.0522

Gnomad AMR exome

AF:

0.0421

Gnomad ASJ exome

AF:

0.0601

Gnomad EAS exome

AF:

0.00651

Gnomad SAS exome

AF:

0.0869

Gnomad FIN exome

AF:

0.0900

Gnomad NFE exome

AF:

0.0817

Gnomad OTH exome

AF:

0.0642

GnomAD4 exome

AF:

0.0786

AC:

104690

AN:

1332108

Hom.:

4367

Cov.:

AF XY:

0.0791

AC XY:

51273

AN XY:

648358

show subpopulations

Gnomad4 AFR exome

AF:

0.0558

Gnomad4 AMR exome

AF:

0.0424

Gnomad4 ASJ exome

AF:

0.0590

Gnomad4 EAS exome

AF:

0.00299

Gnomad4 SAS exome

AF:

0.0884

Gnomad4 FIN exome

AF:

0.0929

Gnomad4 NFE exome

AF:

0.0820

Gnomad4 OTH exome

AF:

0.0746

GnomAD4 genome

AF:

0.0712

AC:

10837

AN:

152248

Hom.:

432

Cov.:

AF XY:

0.0719

AC XY:

5350

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0560

Gnomad4 AMR

AF:

0.0599

Gnomad4 ASJ

AF:

0.0562

Gnomad4 EAS

AF:

0.00580

Gnomad4 SAS

AF:

0.0855

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.0828

Gnomad4 OTH

AF:

0.0768

Alfa

AF:

0.0744

Hom.:

662

Bravo

AF:

0.0669

Asia WGS

AF:

0.0430

AC:

151

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 07, 2012

His992Arg in Exon 19 of TJP2: This variant is not expected to have clinical sign ificance because it has been identified in 6.9% (174/2532) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs77236826). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.42

DANN

Benign

0.23

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