rs9485372

Variant names:

• chr6-149287738-G-A
• rs9485372
• NM_001292035.3:c.6+68962G>A

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+68962G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,064 control chromosomes in the GnomAD database, including 3,265 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 0.20 (3265 hom., cov: 32)
• Consequence: TAB2 NM_001292035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 56 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292035.3	c.6+68962G>A		intron_variant	Intron 2 of 6		NP_001278964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000606202.1	c.-121+68962G>A		intron_variant	Intron 1 of 1	4		ENSP00000476139.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30453 AN: 151946 Hom.: 3267 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.200 AC: 30465 AN: 152064 Hom.: 3265 Cov.: 32 AF XY: 0.201 AC XY: 14972 AN XY: 74308

African (AFR) AF: 0.202 AC: 8383 AN: 41472

American (AMR) AF: 0.181 AC: 2760 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3466

East Asian (EAS) AF: 0.427 AC: 2208 AN: 5168

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4820

European-Finnish (FIN) AF: 0.181 AC: 1914 AN: 10552

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12537 AN: 67998

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.199 Hom.: 7750

Bravo AF: 0.204

Asia WGS AF: 0.331 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.8
DANN	Benign	0.66
PhyloP100		1.1
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: rs9485372; hg19: chr6-149608874; COSMIC: COSV72207680;