rs13301644

Variant names:

• chr9-69174240-C-T
• rs13301644
• ENST00000642889.1:c.447+22469C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201629.3(TJP2):​c.-133C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,501,928 control chromosomes in the GnomAD database, including 143,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14110 hom., cov: 33)
  • Exomes 𝑓: 0.43 (128993 hom.)
• Consequence: TJP2 NM_201629.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.506
• Publications: 11 publications found

Genes affected

ENSG00000285130 (HGNC:):

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 9-69174240-C-T is Benign according to our data. Variant chr9-69174240-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201629.3. 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_201629.3		c.-133C>T		5_prime_UTR	Exon 1 of 21	NP_963923.1	B7Z2R3
	TJP2	NM_001369871.1		c.-127-10847C>T		intron	N/A	NP_001356800.1	Q9UDY2-3
	TJP2	NM_001369870.1		c.-10+22469C>T		intron	N/A	NP_001356799.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000285130	ENST00000642889.1		c.447+22469C>T		intron	N/A	ENSP00000493780.1	A0A2R8YDH4
	TJP2	ENST00000896723.1		c.-133C>T		5_prime_UTR	Exon 1 of 22	ENSP00000566782.1
	TJP2	ENST00000896724.1		c.-133C>T		5_prime_UTR	Exon 1 of 22	ENSP00000566783.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64721 AN: 151880 Hom.: 14086 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.432 AC: 583534 AN: 1349936 Hom.: 128993 Cov.: 36 AF XY: 0.431 AC XY: 283922 AN XY: 658858

African (AFR) AF: 0.343 AC: 10356 AN: 30160

American (AMR) AF: 0.653 AC: 21962 AN: 33646

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 11222 AN: 22882

East Asian (EAS) AF: 0.658 AC: 22413 AN: 34082

South Asian (SAS) AF: 0.388 AC: 28026 AN: 72144

European-Finnish (FIN) AF: 0.470 AC: 21733 AN: 46264

Middle Eastern (MID) AF: 0.468 AC: 2039 AN: 4356

European-Non Finnish (NFE) AF: 0.420 AC: 441094 AN: 1050626

Other (OTH) AF: 0.443 AC: 24689 AN: 55776

GnomAD4 genome AF: 0.426 AC: 64777 AN: 151992 Hom.: 14110 Cov.: 33 AF XY: 0.430 AC XY: 31911 AN XY: 74272

African (AFR) AF: 0.345 AC: 14328 AN: 41502

American (AMR) AF: 0.547 AC: 8365 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3208 AN: 5114

South Asian (SAS) AF: 0.387 AC: 1863 AN: 4816

European-Finnish (FIN) AF: 0.469 AC: 4964 AN: 10576

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 28974 AN: 67908

Other (OTH) AF: 0.465 AC: 983 AN: 2114

Alfa AF: 0.426 Hom.: 1735

Bravo AF: 0.433

Asia WGS AF: 0.535 AC: 1853 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		-0.51
PromoterAI		0.087	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2
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: rs13301644; hg19: chr9-71789156; COSMIC: COSV55270483; COSMIC: COSV55270483;