6-149377814-TAGTC-T

Position:

• chr6-149377814-TAGTC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001292034.3(TAB2):​c.103-201_103-198del 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAB2	NM_001292034.3	c.103-201_103-198del		intron_variant		ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2	c.103-201_103-198del		intron_variant		1	NM_001292034.3	ENSP00000490618	P1

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

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.0873

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.263

Alfa AF: 0.242 Hom.: 475

Bravo AF: 0.233

Asia WGS AF: 0.218 AC: 755 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs34077248; hg19: chr6-149698950;