9-69248208-C-G

Variant names:

• chr9-69248208-C-G
• rs769636686
• NM_004817.4:c.2864C>G

Variant summary

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

The NM_004817.4(TJP2):​c.2864C>G​(p.Pro955Arg) variant causes a missense change involving the alteration of a 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. Synonymous variant affecting the same amino acid position (i.e. P955P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TJP2 NM_004817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71

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 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 rank	MANE	Protein	UniProt
TJP2	NM_004817.4	c.2864C>G	p.Pro955Arg	missense_variant	Exon 19 of 23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.2864C>G	p.Pro955Arg	missense_variant	Exon 19 of 23	1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.3251C>G	p.Pro1084Arg	missense_variant	Exon 21 of 25			ENSP00000493780.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	.;.;.;D;.;D;.;.;.;.;.;.;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Uncertain	0.74	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.1	.;.;.;M;M;M;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.3	.;D;.;.;D;D;.;.;.;D;.;D;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	.;D;.;.;D;D;.;.;.;D;.;D;.
Sift4G	Pathogenic	0.0	.;D;.;.;D;D;.;.;.;D;.;D;.
Polyphen		1.0	.;.;.;D;D;D;.;.;.;.;.;.;.
Vest4		0.77, 0.70, 0.91, 0.74, 0.85
MutPred		0.31		.;.;.;Gain of MoRF binding (P = 0.0158);Gain of MoRF binding (P = 0.0158);Gain of MoRF binding (P = 0.0158);Gain of MoRF binding (P = 0.0158);Gain of MoRF binding (P = 0.0158);.;.;.;.;.;
MVP		0.72
MPC		0.78
ClinPred		0.99	D
GERP RS		6.2
Varity_R		0.74
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs769636686; hg19: chr9-71863124;