rs652921

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001292034.3(TAB2):c.2073G>A(p.Arg691Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.124 in 1,613,838 control chromosomes in the GnomAD database, including 17,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1723 hom., cov: 32)

Exomes 𝑓: 0.12 ( 15959 hom. )

Consequence

TAB2
NM_001292034.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.94

Publications

30 publications found

Variant links:

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

TAB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 6-149409710-G-A is Benign according to our data. Variant chr6-149409710-G-A is described in ClinVar as Benign. ClinVar VariationId is 1241569.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292034.3 link	c.2073G>A	p.Arg691Arg	synonymous_variant	Exon 7 of 7	ENST00000637181.2	NP_001278963.1	Q9NYJ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2 link	c.2073G>A	p.Arg691Arg	synonymous_variant	Exon 7 of 7	1	NM_001292034.3	ENSP00000490618.1		Q9NYJ8-1

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18467

AN:

152022

Hom.:

1721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0597

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.179

AC:

44952

AN:

251346

AF XY:

0.174

show subpopulations

Gnomad AFR exome

AF:

0.0602

Gnomad AMR exome

AF:

0.327

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.125

AC:

182306

AN:

1461698

Hom.:

15959

Cov.:

AF XY:

0.126

AC XY:

91640

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0543

AC:

1819

AN:

33478

American (AMR)

AF:

0.312

AC:

13950

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

3148

AN:

26130

East Asian (EAS)

AF:

0.490

AC:

19437

AN:

39694

South Asian (SAS)

AF:

0.205

AC:

17649

AN:

86248

European-Finnish (FIN)

AF:

0.119

AC:

6344

AN:

53414

Middle Eastern (MID)

AF:

0.126

AC:

724

AN:

5768

European-Non Finnish (NFE)

AF:

0.0996

AC:

110784

AN:

1111862

Other (OTH)

AF:

0.140

AC:

8451

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8487

16973

25460

33946

42433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4390

8780

13170

17560

21950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.121

AC:

18476

AN:

152140

Hom.:

1723

Cov.:

AF XY:

0.128

AC XY:

9482

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0596

AC:

2472

AN:

41494

American (AMR)

AF:

0.210

AC:

3209

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

435

AN:

3470

East Asian (EAS)

AF:

0.512

AC:

2650

AN:

5172

South Asian (SAS)

AF:

0.209

AC:

1007

AN:

4828

European-Finnish (FIN)

AF:

0.122

AC:

1285

AN:

10568

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.105

AC:

7116

AN:

68006

Other (OTH)

AF:

0.125

AC:

264

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

768

1536

2305

3073

3841

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.113

Hom.:

1890

Bravo

AF:

0.129

Asia WGS

AF:

0.324

AC:

1125

AN:

3478

EpiCase

AF:

0.104

EpiControl

AF:

0.104

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 04, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.9

(source)

DANN

Benign

0.62

PhyloP100

3.9

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over