9-69268308-T-C

Variant names:

• chr9-69268308-T-C
• rs1538579
• ENST00000650333.1:c.3339-6099T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000650333.1(TJP2):​c.3339-6099T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,062 control chromosomes in the GnomAD database, including 31,128 homozygotes. 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: 𝑓 0.63 (31128 hom., cov: 32)
• Consequence: TJP2 ENST00000650333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 6 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650333.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP2	ENST00000650333.1		c.3339-6099T>C		intron	N/A	ENSP00000496791.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96131 AN: 151944 Hom.: 31120 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.635

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.632 AC: 96171 AN: 152062 Hom.: 31128 Cov.: 32 AF XY: 0.637 AC XY: 47330 AN XY: 74314

African (AFR) AF: 0.491 AC: 20339 AN: 41442

American (AMR) AF: 0.698 AC: 10679 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2835 AN: 5162

South Asian (SAS) AF: 0.765 AC: 3686 AN: 4820

European-Finnish (FIN) AF: 0.747 AC: 7898 AN: 10566

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.678 AC: 46108 AN: 67994

Other (OTH) AF: 0.635 AC: 1342 AN: 2114

Alfa AF: 0.663 Hom.: 57263

Bravo AF: 0.617

Asia WGS AF: 0.634 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.71
DANN	Benign	0.74
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs1538579; hg19: chr9-71883224;