Genetic Variant TJP2:c.60+54_60+55insAGCGTGAGCGTGAGCGTG (chr9-69174470-T-TCGTGAGCGTGAGCGTGAG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004817.4(TJP2):c.60+54_60+55insAGCGTGAGCGTGAGCGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,364,298 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

TJP2
NM_004817.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

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: Orphanet, Ambry Genetics
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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004817.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TJP2	NM_004817.4	MANE Select	c.60+54_60+55insAGCGTGAGCGTGAGCGTG	intron	N/A	NP_004808.2
TJP2	NM_001369871.1		c.-127-10601_-127-10600insAGCGTGAGCGTGAGCGTG	intron	N/A	NP_001356800.1	Q9UDY2-3
TJP2	NM_001369870.1		c.-10+22715_-10+22716insAGCGTGAGCGTGAGCGTG	intron	N/A	NP_001356799.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TJP2	ENST00000377245.9	TSL:1 MANE Select	c.60+54_60+55insAGCGTGAGCGTGAGCGTG	intron	N/A	ENSP00000366453.4	Q9UDY2-1
ENSG00000285130	ENST00000642889.1		c.447+22715_447+22716insAGCGTGAGCGTGAGCGTG	intron	N/A	ENSP00000493780.1	A0A2R8YDH4
TJP2	ENST00000348208.9	TSL:1	c.60+54_60+55insAGCGTGAGCGTGAGCGTG	intron	N/A	ENSP00000345893.4	Q9UDY2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1364298

Hom.:

Cov.:

AF XY:

0.00000445

AC XY:

AN XY:

674420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30978

American (AMR)

AF:

0.00

AC:

AN:

35370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24914

East Asian (EAS)

AF:

0.0000284

AC:

AN:

35268

South Asian (SAS)

AF:

0.00

AC:

AN:

78378

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4650

European-Non Finnish (NFE)

AF:

0.00000286

AC:

AN:

1049220

Other (OTH)

AF:

0.0000176

AC:

AN:

56666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.44

Splicing

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

Publications

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9-69174470-TCGTGAG-TCGTGAGCGTGAGCGTGAGCGTGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over