9-69234419-C-T

Position:

• chr9-69234419-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004817.4(TJP2):​c.1672-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.022 (0 hom., cov: 23)
  • Exomes 𝑓: 0.041 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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]

ENSG00000285130 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.1672-20C>T		intron_variant		ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.1672-20C>T		intron_variant		1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.2059-20C>T		intron_variant				ENSP00000493780.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1945 AN: 86400 Hom.: 0 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.0314

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00532

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0170

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0405 AC: 29813 AN: 735530 Hom.: 0 Cov.: 17 AF XY: 0.0428 AC XY: 16162 AN XY: 377330

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.0892

Gnomad4 ASJ exome AF: 0.0470

Gnomad4 EAS exome AF: 0.0497

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.0473

Gnomad4 NFE exome AF: 0.0293

Gnomad4 OTH exome AF: 0.0417

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0225 AC: 1945 AN: 86466 Hom.: 0 Cov.: 23 AF XY: 0.0207 AC XY: 880 AN XY: 42528

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.0168

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.0165

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0176

Alfa AF: 0.0244 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.2
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs80014470; hg19: chr9-71849335;