chr6-149377814-TAGTC-T

Variant names:

• chr6-149377814-TAGTC-T
• rs34077248
• NM_001292034.3:c.103-201_103-198delTCAG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001292034.3(TAB2):​c.103-201_103-198delTCAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,048 control chromosomes in the GnomAD database, including 4,358 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4358 hom., cov: 24)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980
• 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: Laboratory for Molecular Medicine, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
• polyvalvular heart disease syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-149377814-TAGTC-T is Benign according to our data. Variant chr6-149377814-TAGTC-T is described in ClinVar as Benign. ClinVar VariationId is 1234365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	NM_001292034.3	MANE Select	c.103-201_103-198delTCAG		intron	N/A	NP_001278963.1	Q9NYJ8-1
	TAB2	NM_001369506.1		c.103-201_103-198delTCAG		intron	N/A	NP_001356435.1	Q9NYJ8-1
	TAB2	NM_015093.6		c.103-201_103-198delTCAG		intron	N/A	NP_055908.1	Q9NYJ8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000637181.2	TSL:1 MANE Select	c.103-203_103-200delAGTC		intron	N/A	ENSP00000490618.1	Q9NYJ8-1
	TAB2	ENST00000470466.5	TSL:1	n.103-203_103-200delAGTC		intron	N/A	ENSP00000432709.1	Q9NYJ8-2
	TAB2	ENST00000367456.5	TSL:5	c.103-203_103-200delAGTC		intron	N/A	ENSP00000356426.1	Q9NYJ8-1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35581 AN: 151930 Hom.: 4348 Cov.: 24

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.234 AC: 35619 AN: 152048 Hom.: 4358 Cov.: 24 AF XY: 0.232 AC XY: 17220 AN XY: 74324

African (AFR) AF: 0.220 AC: 9105 AN: 41470

American (AMR) AF: 0.213 AC: 3255 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 969 AN: 3468

East Asian (EAS) AF: 0.0873 AC: 452 AN: 5176

South Asian (SAS) AF: 0.190 AC: 912 AN: 4812

European-Finnish (FIN) AF: 0.248 AC: 2618 AN: 10566

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.257 AC: 17489 AN: 67952

Other (OTH) AF: 0.263 AC: 556 AN: 2114

Alfa AF: 0.242 Hom.: 475

Bravo AF: 0.233

Asia WGS AF: 0.218 AC: 755 AN: 3468

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.098
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: rs34077248; hg19: chr6-149698950;