Genetic Variant TJP2:n.64G>A (chr9-69174357-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000636247.1(TJP2):n.64G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

TJP2
ENST00000636247.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0550

Publications

0 publications found

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 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)

TJP2 links:

ENSG00000285130 (HGNC:):

ENSG00000285130 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636247.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TJP2	NM_004817.4	MANE Select	c.-16G>A	5_prime_UTR	Exon 1 of 23	NP_004808.2
TJP2	NM_001369872.1		c.-16G>A	5_prime_UTR	Exon 1 of 22	NP_001356801.1
TJP2	NM_001369873.1		c.-16G>A	5_prime_UTR	Exon 1 of 21	NP_001356802.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TJP2	ENST00000636247.1	TSL:1	n.64G>A	non_coding_transcript_exon	Exon 1 of 19
TJP2	ENST00000377245.9	TSL:1 MANE Select	c.-16G>A	5_prime_UTR	Exon 1 of 23	ENSP00000366453.4
TJP2	ENST00000348208.9	TSL:1	c.-16G>A	5_prime_UTR	Exon 1 of 21	ENSP00000345893.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399214

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

690188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31646

American (AMR)

AF:

0.00

AC:

AN:

35724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25166

East Asian (EAS)

AF:

0.00

AC:

AN:

35770

South Asian (SAS)

AF:

0.00

AC:

AN:

79254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078944

Other (OTH)

AF:

0.00

AC:

AN:

57980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.055

PromoterAI

0.045

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over