Variant 6-149409710-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
TAB2	NM_001292034.3 linkuse as main transcript	c.2073G>A	p.Arg691Arg	synonymous_variant	7/7	ENST00000637181.2	NP_001278963.1	Q9NYJ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2 linkuse as main transcript	c.2073G>A	p.Arg691Arg	synonymous_variant	7/7	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

GnomAD3 exomes

AF:

0.179

AC:

44952

AN:

251346

Hom.:

6139

AF XY:

0.174

AC XY:

23602

AN XY:

135836

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 SAS exome

AF:

0.208

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

Gnomad4 AFR exome

AF:

0.0543

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.0996

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.121

AC:

18476

AN:

152140

Hom.:

1723

Cov.:

AF XY:

0.128

AC XY:

9482

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0596

Gnomad4 AMR

AF:

0.210

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.112

Hom.:

1475

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.9

DANN

Benign

0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over