chr6-149370155-AT-A

Position:

• chr6-149370155-AT-A

Variant summary

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

The NM_001292034.3(TAB2):​c.102+58del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,441,954 control chromosomes in the GnomAD database, including 16,450 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1743 hom., cov: 30)
  • Exomes 𝑓: 0.13 (14707 hom.)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0220

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 6-149370155-AT-A is Benign according to our data. Variant chr6-149370155-AT-A is described in ClinVar as [Benign]. Clinvar id is 1235661.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAB2	NM_001292034.3	c.102+58del		intron_variant		ENST00000637181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAB2	ENST00000637181.2	c.102+58del		intron_variant		1	NM_001292034.3	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18593 AN: 152068 Hom.: 1739 Cov.: 30

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.126 AC: 161915 AN: 1289768 Hom.: 14707 AF XY: 0.127 AC XY: 82522 AN XY: 649920

Gnomad4 AFR exome AF: 0.0569

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0976

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.122 AC: 18606 AN: 152186 Hom.: 1743 Cov.: 30 AF XY: 0.128 AC XY: 9551 AN XY: 74418

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.126

Alfa AF: 0.115 Hom.: 157

Bravo AF: 0.130

Asia WGS AF: 0.331 AC: 1147 AN: 3478

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

Sep 06, 2018

- -

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: rs35974009; hg19: chr6-149691291;