rs652921

chr6-149409710-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001292034.3(TAB2):c.2073G>A(p.Arg691=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.94

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]

ACMG classification

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	UniProt
TAB2	NM_001292034.3	c.2073G>A	p.Arg691=	synonymous_variant	7/7	ENST00000637181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB2	ENST00000637181.2	c.2073G>A	p.Arg691=	synonymous_variant	7/7	1	NM_001292034.3	P1
TAB2	ENST00000470466.5	c.*672G>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	1
TAB2	ENST00000367456.5	c.2073G>A	p.Arg691=	synonymous_variant	8/8	5		P1
TAB2	ENST00000636456.1	c.1221G>A	p.Arg407=	synonymous_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18467 AN: 152022 Hom.: 1721 Cov.: 32

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

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.: 32 AF XY: 0.126 AC XY: 91640 AN XY: 727150

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.: 32 AF XY: 0.128 AC XY: 9482 AN XY: 74356

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	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

Other links and lift over

dbSNP: rs652921; hg19: chr6-149730846; COSMIC: COSV53851469; COSMIC: COSV53851469;