9-69151771-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000636438.1(TJP2):c.237G>A(p.Gln79=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.000459 in 1,232,092 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: TJP2 ENST00000636438.1 splice_region, synonymous
• Scores: Splicing: ADA: 0.01170
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

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 Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TJP2	NM_001170414.2	c.-10G>A		splice_region_variant, 5_prime_UTR_variant	2/22
TJP2	NM_001369870.1	c.-10G>A		splice_region_variant, 5_prime_UTR_variant	2/24
TJP2	NM_001369871.1	c.-128G>A		splice_region_variant, 5_prime_UTR_variant	2/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TJP2	ENST00000636438.1	c.237G>A	p.Gln79=	splice_region_variant, synonymous_variant	2/24	5		A2
TJP2	ENST00000423935.6	c.-10G>A		splice_region_variant, 5_prime_UTR_variant	2/6	2
TJP2	ENST00000606364.5	c.-10G>A		splice_region_variant, 5_prime_UTR_variant	2/6	4

Frequencies

GnomAD3 genomes AF: 0.00228 AC: 347 AN: 152150 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00780

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00240

GnomAD4 exome AF: 0.000201 AC: 217 AN: 1079824 Hom.: 1 Cov.: 30 AF XY: 0.000202 AC XY: 103 AN XY: 509758

Gnomad4 AFR exome AF: 0.00806

Gnomad4 AMR exome AF: 0.000475

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: 0.00000109

Gnomad4 OTH exome AF: 0.000618

GnomAD4 genome AF: 0.00229 AC: 348 AN: 152268 Hom.: 1 Cov.: 32 AF XY: 0.00235 AC XY: 175 AN XY: 74446

Gnomad4 AFR AF: 0.00780

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.000417 Hom.: 0

Bravo AF: 0.00280

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 17, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	19
Dann	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.012
dbscSNV1_RF	Benign	0.030

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

Publications

LitVar

Other links and lift over

dbSNP: rs374563251; hg19: chr9-71766687;