rs12340440

Positions:

• chr9-69236164-C-A
• chr9-69236164-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004817.4(TJP2):​c.1917C>A​(p.Asp639Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TJP2 NM_004817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TJP2	NM_004817.4	c.1917C>A	p.Asp639Glu	missense_variant	13/23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.1917C>A	p.Asp639Glu	missense_variant	13/23	1	NM_004817.4	ENSP00000366453	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;.;.;.;T;.;T;.;.;.;.;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.91	D;D;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.47	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;.;.;L;L;L;.;.;.;.;.;.;.
MutationTaster	Benign	0.000024	P;P;P;P;P;P
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.3	.;N;.;.;.;N;N;.;.;.;N;.;N;.
REVEL	Benign	0.23
Sift	Benign	0.051	.;T;.;.;.;D;D;.;.;.;D;.;D;.
Sift4G	Benign	0.11	.;T;.;.;.;T;T;.;.;.;T;.;T;.
Polyphen		1.0, 1.0	.;.;.;.;D;D;D;.;.;.;.;.;.;.
Vest4		0.57, 0.57, 0.56, 0.57, 0.53
MutPred		0.45		.;.;.;.;Loss of ubiquitination at K641 (P = 0.0982);Loss of ubiquitination at K641 (P = 0.0982);Loss of ubiquitination at K641 (P = 0.0982);Loss of ubiquitination at K641 (P = 0.0982);Loss of ubiquitination at K641 (P = 0.0982);.;.;.;.;.;
MVP		0.63
MPC		0.71
ClinPred		0.94	D
GERP RS		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.36

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: rs12340440; hg19: chr9-71851080;