9-69174470-TCGTGAG-TCGTGAGCGTGAG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004817.4(TJP2):​c.60+49_60+54dupAGCGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,514,898 control chromosomes in the GnomAD database, including 141,229 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (13800 hom., cov: 0)
  • Exomes 𝑓: 0.42 (127429 hom.)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.440
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-69174470-T-TCGTGAG is Benign according to our data. Variant chr9-69174470-T-TCGTGAG is described in ClinVar as Benign. ClinVar VariationId is 682800.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

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+54dupAGCGTG		intron	N/A	NP_004808.2
	TJP2	NM_001369871.1		c.-127-10606_-127-10601dupAGCGTG		intron	N/A	NP_001356800.1	Q9UDY2-3
	TJP2	NM_001369870.1		c.-10+22710_-10+22715dupAGCGTG		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+54dupAGCGTG		intron	N/A	ENSP00000366453.4	Q9UDY2-1
	ENSG00000285130	ENST00000642889.1		c.447+22710_447+22715dupAGCGTG		intron	N/A	ENSP00000493780.1	A0A2R8YDH4
	TJP2	ENST00000348208.9	TSL:1	c.60+49_60+54dupAGCGTG		intron	N/A	ENSP00000345893.4	Q9UDY2-2

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64070 AN: 151146 Hom.: 13775 Cov.: 0

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.457

GnomAD2 exomes AF: 0.470 AC: 70604 AN: 150138 AF XY: 0.461

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.658

Gnomad ASJ exome AF: 0.493

Gnomad EAS exome AF: 0.614

Gnomad FIN exome AF: 0.473

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.423 AC: 576545 AN: 1363634 Hom.: 127429 Cov.: 28 AF XY: 0.422 AC XY: 284665 AN XY: 674150

African (AFR) AF: 0.335 AC: 10361 AN: 30962

American (AMR) AF: 0.645 AC: 22822 AN: 35360

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 12139 AN: 24902

East Asian (EAS) AF: 0.653 AC: 23017 AN: 35260

South Asian (SAS) AF: 0.384 AC: 30096 AN: 78362

European-Finnish (FIN) AF: 0.466 AC: 22784 AN: 48852

Middle Eastern (MID) AF: 0.450 AC: 2094 AN: 4650

European-Non Finnish (NFE) AF: 0.409 AC: 428690 AN: 1048642

Other (OTH) AF: 0.433 AC: 24542 AN: 56644

GnomAD4 genome AF: 0.424 AC: 64135 AN: 151264 Hom.: 13800 Cov.: 0 AF XY: 0.427 AC XY: 31515 AN XY: 73810

African (AFR) AF: 0.344 AC: 14210 AN: 41296

American (AMR) AF: 0.544 AC: 8278 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1684 AN: 3458

East Asian (EAS) AF: 0.622 AC: 3128 AN: 5026

South Asian (SAS) AF: 0.386 AC: 1850 AN: 4796

European-Finnish (FIN) AF: 0.465 AC: 4857 AN: 10448

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28769 AN: 67738

Other (OTH) AF: 0.462 AC: 971 AN: 2102

Alfa AF: 0.342 Hom.: 1332

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV55271422;