chr9-69174470-TCGTGAG-T

Variant names:

• chr9-69174470-TCGTGAG-T
• rs59568063
• NM_004817.4:c.60+49_60+54delAGCGTG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004817.4(TJP2):​c.60+49_60+54delAGCGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,364,282 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73
• Publications: 3 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: 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)

ENSG00000285130 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP2	NM_004817.4	MANE Select	c.60+49_60+54delAGCGTG		intron	N/A	NP_004808.2
	TJP2	NM_001369871.1		c.-127-10606_-127-10601delAGCGTG		intron	N/A	NP_001356800.1	Q9UDY2-3
	TJP2	NM_001369870.1		c.-10+22710_-10+22715delAGCGTG		intron	N/A	NP_001356799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TJP2	ENST00000377245.9	TSL:1 MANE Select	c.60+49_60+54delAGCGTG		intron	N/A	ENSP00000366453.4	Q9UDY2-1
	ENSG00000285130	ENST00000642889.1		c.447+22710_447+22715delAGCGTG		intron	N/A	ENSP00000493780.1	A0A2R8YDH4
	TJP2	ENST00000348208.9	TSL:1	c.60+49_60+54delAGCGTG		intron	N/A	ENSP00000345893.4	Q9UDY2-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1364282 Hom.: 0 AF XY: 0.00000148 AC XY: 1 AN XY: 674414

African (AFR) AF: 0.00 AC: 0 AN: 30978

American (AMR) AF: 0.00 AC: 0 AN: 35368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24914

East Asian (EAS) AF: 0.0000567 AC: 2 AN: 35264

South Asian (SAS) AF: 0.00 AC: 0 AN: 78378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4650

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1049210

Other (OTH) AF: 0.00 AC: 0 AN: 56666

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

Other links and lift over

dbSNP: rs59568063; hg19: chr9-71789386;