9-69197087-C-G

Variant summary

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

The NM_004817.4(TJP2):c.61-15461C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,012 control chromosomes in the GnomAD database, including 65,552 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 0.93 (65552 hom., cov: 28)
• Consequence: TJP2 NM_004817.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484

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 (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_004817.4	c.61-15461C>G		intron_variant		ENST00000377245.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000377245.9	c.61-15461C>G		intron_variant		1	NM_004817.4	P2

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141052 AN: 151894 Hom.: 65488 Cov.: 28

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.935

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.924

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.929 AC: 141175 AN: 152012 Hom.: 65552 Cov.: 28 AF XY: 0.930 AC XY: 69097 AN XY: 74306

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.926

Gnomad4 EAS AF: 0.935

Gnomad4 SAS AF: 0.917

Gnomad4 FIN AF: 0.947

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.924

Alfa AF: 0.926 Hom.: 8114

Bravo AF: 0.927

Asia WGS AF: 0.913 AC: 3173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.78
Dann	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10481782; hg19: chr9-71812003;