6-149272784-C-T

Variant names:

• chr6-149272784-C-T
• rs727979
• NM_001292035.3:c.6+54008C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001292035.3(TAB2):​c.6+54008C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,168 control chromosomes in the GnomAD database, including 2,305 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2305 hom., cov: 32)
• Consequence: TAB2 NM_001292035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 10 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: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• polyvalvular heart disease syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001292035.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	NM_001292035.3		c.6+54008C>T		intron	N/A	NP_001278964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAB2	ENST00000606202.1	TSL:4	c.-121+54008C>T		intron	N/A	ENSP00000476139.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25788 AN: 152050 Hom.: 2303 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.170 AC: 25809 AN: 152168 Hom.: 2305 Cov.: 32 AF XY: 0.173 AC XY: 12882 AN XY: 74386

African (AFR) AF: 0.151 AC: 6275 AN: 41524

American (AMR) AF: 0.235 AC: 3599 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1173 AN: 5162

South Asian (SAS) AF: 0.213 AC: 1031 AN: 4830

European-Finnish (FIN) AF: 0.211 AC: 2234 AN: 10578

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10504 AN: 67994

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.162 Hom.: 4046

Bravo AF: 0.174

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs727979; hg19: chr6-149593920;