rs267607101
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP2PP5BP4
The NM_001292034.3(TAB2):c.622C>T(p.Pro208Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
TAB2
NM_001292034.3 missense
NM_001292034.3 missense
Scores
2
2
10
Clinical Significance
Conservation
PhyloP100: 4.56
Genes affected
TAB2 (HGNC:17075): (TGF-beta activated kinase 1 (MAP3K7) binding protein 2) The protein encoded by this gene is an activator of MAP3K7/TAK1, which is required for for the IL-1 induced activation of nuclear factor kappaB and MAPK8/JNK. This protein forms a kinase complex with TRAF6, MAP3K7 and TAB1, and it thus serves as an adaptor that links MAP3K7 and TRAF6. This protein, along with TAB1 and MAP3K7, also participates in the signal transduction induced by TNFSF11/RANKl through the activation of the receptor activator of NF-kappaB (TNFRSF11A/RANK), which may regulate the development and function of osteoclasts. Studies of the related mouse protein indicate that it functions to protect against liver damage caused by chemical stressors. Mutations in this gene cause congenital heart defects, multiple types, 2 (CHTD2). Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, TAB2
PP5
?
Variant 6-149378537-C-T is Pathogenic according to our data. Variant chr6-149378537-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 5211.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-149378537-C-T is described in Lovd as [Pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18136942).. Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAB2 | NM_001292034.3 | c.622C>T | p.Pro208Ser | missense_variant | 3/7 | ENST00000637181.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAB2 | ENST00000637181.2 | c.622C>T | p.Pro208Ser | missense_variant | 3/7 | 1 | NM_001292034.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251342Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135844
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461800Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727206
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GnomAD4 genome ? Cov.: 32
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Cov.:
32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital heart defects, multiple types, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 11, 2010 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
Polyphen
B;B;B
Vest4
0.75, 0.71
MutPred
Gain of glycosylation at P208 (P = 0.0545);Gain of glycosylation at P208 (P = 0.0545);Gain of glycosylation at P208 (P = 0.0545);
MVP
0.98
MPC
0.32
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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