rs2789488

Variant names:

• chr6-149404154-G-A
• rs2789488
• NM_001292034.3:c.1939+4970G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292034.3(TAB2):​c.1939+4970G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,936 control chromosomes in the GnomAD database, including 15,602 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15602 hom., cov: 32)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.878
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292034.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	NM_001292034.3	MANE Select	c.1939+4970G>A		intron	N/A	NP_001278963.1
	TAB2	NM_001369506.1		c.1939+4970G>A		intron	N/A	NP_001356435.1
	TAB2	NM_015093.6		c.1939+4970G>A		intron	N/A	NP_055908.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000637181.2	TSL:1 MANE Select	c.1939+4970G>A		intron	N/A	ENSP00000490618.1
	TAB2	ENST00000470466.5	TSL:1	n.*538+4970G>A		intron	N/A	ENSP00000432709.1
	TAB2	ENST00000367456.5	TSL:5	c.1939+4970G>A		intron	N/A	ENSP00000356426.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67653 AN: 151818 Hom.: 15580 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67726 AN: 151936 Hom.: 15602 Cov.: 32 AF XY: 0.448 AC XY: 33276 AN XY: 74260

African (AFR) AF: 0.546 AC: 22611 AN: 41422

American (AMR) AF: 0.455 AC: 6947 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1455 AN: 3466

East Asian (EAS) AF: 0.603 AC: 3111 AN: 5162

South Asian (SAS) AF: 0.501 AC: 2415 AN: 4822

European-Finnish (FIN) AF: 0.407 AC: 4276 AN: 10518

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25623 AN: 67956

Other (OTH) AF: 0.455 AC: 959 AN: 2110

Alfa AF: 0.431 Hom.: 2334

Bravo AF: 0.458

Asia WGS AF: 0.602 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.51
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

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: rs2789488; hg19: chr6-149725290;