Variant chr9-69234419-C-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.1672-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 96,294 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 241 hom., cov: 23)

Exomes 𝑓: 0.084 ( 1739 hom. )

Failed GnomAD Quality Control

Consequence

TJP2
NM_004817.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.589

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 9-69234419-C-G is Benign according to our data. Variant chr9-69234419-C-G is described in ClinVar as [Benign]. Clinvar id is 259551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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.1672-20C>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.1672-20C>G		intron_variant		1	NM_004817.4	ENSP00000366453.4		Q9UDY2-1
ENSG00000285130	ENST00000642889.1 linkuse as main transcript	c.2059-20C>G		intron_variant				ENSP00000493780.1		A0A2R8YDH4

Frequencies

GnomAD3 genomes

AF:

0.0927

AC:

8921

AN:

96224

Hom.:

240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0796

Gnomad AMR

AF:

0.0747

Gnomad ASJ

AF:

0.0594

Gnomad EAS

AF:

0.00919

Gnomad SAS

AF:

0.0975

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0556

Gnomad NFE

AF:

0.0905

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.0741

AC:

11239

AN:

151634

Hom.:

351

AF XY:

0.0771

AC XY:

6474

AN XY:

83986

show subpopulations

Gnomad AFR exome

AF:

0.0908

Gnomad AMR exome

AF:

0.0484

Gnomad ASJ exome

AF:

0.0613

Gnomad EAS exome

AF:

0.00904

Gnomad SAS exome

AF:

0.0940

Gnomad FIN exome

AF:

0.109

Gnomad NFE exome

AF:

0.0746

Gnomad OTH exome

AF:

0.0719

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0840

AC:

63167

AN:

752188

Hom.:

1739

Cov.:

AF XY:

0.0847

AC XY:

32738

AN XY:

386632

show subpopulations

Gnomad4 AFR exome

AF:

0.0987

Gnomad4 AMR exome

AF:

0.0470

Gnomad4 ASJ exome

AF:

0.0607

Gnomad4 EAS exome

AF:

0.00366

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.0871

Gnomad4 OTH exome

AF:

0.0810

GnomAD4 genome

AF:

0.0927

AC:

8926

AN:

96294

Hom.:

241

Cov.:

AF XY:

0.0936

AC XY:

4375

AN XY:

46750

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0745

Gnomad4 ASJ

AF:

0.0594

Gnomad4 EAS

AF:

0.00890

Gnomad4 SAS

AF:

0.0982

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.0905

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.00955

Hom.:

Bravo

AF:

0.0590

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 15, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 14, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.3

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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