rs41277901
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004817.4(TJP2):c.1478G>A(p.Arg493Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00335 in 1,614,078 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 44 hom. )
Consequence
TJP2
NM_004817.4 missense
NM_004817.4 missense
Scores
1
11
Clinical Significance
Conservation
PhyloP100: 4.23
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0020357668).
BP6
?
Variant 9-69229208-G-A is Benign according to our data. Variant chr9-69229208-G-A is described in ClinVar as [Benign]. Clinvar id is 44092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1856/152256) while in subpopulation AFR AF= 0.036 (1497/41536). AF 95% confidence interval is 0.0345. There are 26 homozygotes in gnomad4. There are 910 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 26 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TJP2 | NM_004817.4 | c.1478G>A | p.Arg493Lys | missense_variant | 10/23 | ENST00000377245.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TJP2 | ENST00000377245.9 | c.1478G>A | p.Arg493Lys | missense_variant | 10/23 | 1 | NM_004817.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0122 AC: 1854AN: 152138Hom.: 26 Cov.: 32
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GnomAD3 exomes AF: 0.00468 AC: 1177AN: 251486Hom.: 12 AF XY: 0.00394 AC XY: 535AN XY: 135918
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GnomAD4 exome AF: 0.00243 AC: 3547AN: 1461822Hom.: 44 Cov.: 31 AF XY: 0.00226 AC XY: 1645AN XY: 727226
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GnomAD4 genome ? AF: 0.0122 AC: 1856AN: 152256Hom.: 26 Cov.: 32 AF XY: 0.0122 AC XY: 910AN XY: 74448
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ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Arg470Lys in Exon 11 of TJP2: This variant is not expected to have clinical sign ificance because it has been identified in 3.6% (134/3738) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs41277901). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 22, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;D;.;D;D;D;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
Polyphen
0.0070, 0.0040
.;.;.;.;B;B;B;.;.;.;.;.;.;.
Vest4
0.23, 0.25, 0.26, 0.24
MVP
0.40
MPC
0.20
ClinPred
T
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at