rs11145465

Positions:

• chr9-69151677-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636438.1(TJP2):​c.143C>A​(p.Ser48Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.204 in 1,231,738 control chromosomes in the GnomAD database, including 26,683 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 0.19 (2736 hom., cov: 31)
  • Exomes 𝑓: 0.21 (23947 hom.)
• Consequence: TJP2 ENST00000636438.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.46

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018132925).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_001170414.2	c.-104C>A		5_prime_UTR_variant	2/22
TJP2	NM_001369870.1	c.-104C>A		5_prime_UTR_variant	2/24
TJP2	NM_001369871.1	c.-222C>A		5_prime_UTR_variant	2/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000636438.1	c.143C>A	p.Ser48Tyr	missense_variant	2/24	5		A2
TJP2	ENST00000423935.6	c.-104C>A		5_prime_UTR_variant	2/6	2
TJP2	ENST00000606364.5	c.-104C>A		5_prime_UTR_variant	2/6	4

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28403 AN: 151866 Hom.: 2736 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.221

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.206 AC: 222643 AN: 1079754 Hom.: 23947 Cov.: 31 AF XY: 0.207 AC XY: 105263 AN XY: 509744

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.132

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.00422

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.187 AC: 28408 AN: 151984 Hom.: 2736 Cov.: 31 AF XY: 0.184 AC XY: 13650 AN XY: 74284

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.00831

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.169

Alfa AF: 0.196 Hom.: 1672

Bravo AF: 0.184

TwinsUK AF: 0.227 AC: 841

ALSPAC AF: 0.209 AC: 805

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Benign	0.83
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.56	T;T;T
MetaRNN	Benign	0.0018	T;T;T
MutationTaster	Benign	4.8e-31	P;P
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11145465; hg19: chr9-71766593;