9-69216482-T-C

Variant names:

• chr9-69216482-T-C
• rs2498417
• NM_004817.4:c.239+19T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004817.4(TJP2):​c.239+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,613,654 control chromosomes in the GnomAD database, including 678,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.90 (62408 hom., cov: 31)
  • Exomes 𝑓: 0.92 (615996 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.10
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• cholestasis, progressive familial intrahepatic, 4

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet
• familial hypercholanemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• hypercholanemia, familial 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000285130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-69216482-T-C is Benign according to our data. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-69216482-T-C is described in CliVar as Benign. Clinvar id is 196398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4	c.239+19T>C		intron_variant	Intron 3 of 22	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.239+19T>C		intron_variant	Intron 3 of 22	1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.626+19T>C		intron_variant	Intron 5 of 24			ENSP00000493780.1

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137622 AN: 152098 Hom.: 62355 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.897

GnomAD2 exomes AF: 0.921 AC: 231402 AN: 251284 AF XY: 0.923

Gnomad AFR exome AF: 0.863

Gnomad AMR exome AF: 0.916

Gnomad ASJ exome AF: 0.928

Gnomad EAS exome AF: 0.934

Gnomad FIN exome AF: 0.948

Gnomad NFE exome AF: 0.923

Gnomad OTH exome AF: 0.915

GnomAD4 exome AF: 0.918 AC: 1341499 AN: 1461438 Hom.: 615996 Cov.: 49 AF XY: 0.919 AC XY: 668196 AN XY: 727020

African (AFR) AF: 0.867 AC: 29029 AN: 33472

American (AMR) AF: 0.915 AC: 40899 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 24269 AN: 26132

East Asian (EAS) AF: 0.943 AC: 37449 AN: 39698

South Asian (SAS) AF: 0.923 AC: 79615 AN: 86240

European-Finnish (FIN) AF: 0.946 AC: 50513 AN: 53394

Middle Eastern (MID) AF: 0.938 AC: 5151 AN: 5492

European-Non Finnish (NFE) AF: 0.917 AC: 1019567 AN: 1111926

Other (OTH) AF: 0.911 AC: 55007 AN: 60362

GnomAD4 genome AF: 0.905 AC: 137733 AN: 152216 Hom.: 62408 Cov.: 31 AF XY: 0.907 AC XY: 67529 AN XY: 74436

African (AFR) AF: 0.863 AC: 35809 AN: 41486

American (AMR) AF: 0.898 AC: 13715 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3207 AN: 3472

East Asian (EAS) AF: 0.934 AC: 4846 AN: 5188

South Asian (SAS) AF: 0.918 AC: 4426 AN: 4822

European-Finnish (FIN) AF: 0.946 AC: 10043 AN: 10618

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62692 AN: 68032

Other (OTH) AF: 0.897 AC: 1897 AN: 2114

Alfa AF: 0.915 Hom.: 11849

Bravo AF: 0.899

Asia WGS AF: 0.904 AC: 3145 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Jan 29, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cholestasis, progressive familial intrahepatic, 4 Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypercholanemia, familial 1 Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.21
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2498417; hg19: chr9-71831398;