chr9-69174015-C-G

Variant names:

• chr9-69174015-C-G
• ENST00000642889.1:c.447+22244C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369871.1(TJP2):​c.-127-11072C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 867,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: TJP2 NM_001369871.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_001369871.1	c.-127-11072C>G		intron_variant	Intron 2 of 24		NP_001356800.1
TJP2	NM_001369870.1	c.-10+22244C>G		intron_variant	Intron 2 of 23		NP_001356799.1
TJP2	NM_001170414.2	c.-10+22244C>G		intron_variant	Intron 2 of 21		NP_001163885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285130	ENST00000642889.1	c.447+22244C>G		intron_variant	Intron 3 of 24			ENSP00000493780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000231 AC: 2 AN: 867120 Hom.: 0 Cov.: 29 AF XY: 0.00000249 AC XY: 1 AN XY: 402068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000255

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.2
DANN	Benign	0.78

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-71788931;