9-69228107-C-G

Variant names:

• chr9-69228107-C-G
• rs2309428
• NM_004817.4:c.1446C>G

Variant summary

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

The NM_004817.4(TJP2):​c.1446C>G​(p.Asp482Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in Lovd.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TJP2 NM_004817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02447769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TJP2	NM_004817.4	c.1446C>G	p.Asp482Glu	missense_variant	Exon 9 of 23	ENST00000377245.9	NP_004808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TJP2	ENST00000377245.9	c.1446C>G	p.Asp482Glu	missense_variant	Exon 9 of 23	1	NM_004817.4	ENSP00000366453.4
ENSG00000285130	ENST00000642889.1	c.1833C>G	p.Asp611Glu	missense_variant	Exon 11 of 25			ENSP00000493780.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.9
DANN	Benign	0.19
DEOGEN2	Benign	0.11	.;.;.;.;T;.;T;.;.;.;.;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.51	T;T;T;T;.;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.024	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.48	.;.;.;.;N;N;N;.;.;.;.;.;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.080	.;N;.;.;.;N;N;.;.;.;N;.;N;.
REVEL	Benign	0.014
Sift	Benign	1.0	.;T;.;.;.;T;T;.;.;.;T;.;T;.
Sift4G	Benign	1.0	.;T;.;.;.;T;T;.;.;.;T;.;T;.
Polyphen		0.0	.;.;.;.;B;B;B;.;.;.;.;.;.;.
Vest4		0.038, 0.023, 0.040, 0.063
MutPred		0.21		.;.;.;.;Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);Gain of glycosylation at P484 (P = 0.0859);.;.;.;.;.;
MVP		0.36
MPC		0.18
ClinPred		0.028	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.12

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: rs2309428; hg19: chr9-71843023;