rs878961826

Variant names:

• chr6-149370015-C-A
• rs878961826
• NM_001292034.3:c.18C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-149370015-C-A
• chr6-149370015-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001292034.3(TAB2):​c.18C>A​(p.His6Gln) 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. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H6R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAB2 NM_001292034.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

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]

TAB2 Gene-Disease associations (from GenCC):

• chromosome 6q24-q25 deletion syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• congenital heart defects, multiple types, 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• polyvalvular heart disease syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12970743).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292034.3	c.18C>A	p.His6Gln	missense_variant	Exon 2 of 7	ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2	c.18C>A	p.His6Gln	missense_variant	Exon 2 of 7	1	NM_001292034.3	ENSP00000490618.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.12	T;T;T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	0.041
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	.;T;.;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N;.;N;N
PhyloP100		2.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.48	.;.;N;N
REVEL	Benign	0.096
Sift	Benign	0.54	.;.;T;T
Sift4G	Benign	0.37	.;T;T;T
Polyphen		0.0010	B;.;B;B
Vest4		0.10, 0.10
MutPred		0.26		Gain of disorder (P = 0.0956);Gain of disorder (P = 0.0956);Gain of disorder (P = 0.0956);Gain of disorder (P = 0.0956);
MVP		0.51
MPC		0.31
ClinPred		0.67	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.34
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs878961826; hg19: chr6-149691151;