NM_001292034.3:c.103-252G>T

Variant names:

• chr6-149377766-G-T
• rs6916134
• NM_001292034.3:c.103-252G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001292034.3(TAB2):​c.103-252G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,202 control chromosomes in the GnomAD database, including 60,250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60250 hom., cov: 32)
• Consequence: TAB2 NM_001292034.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.268
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 6-149377766-G-T is Benign according to our data. Variant chr6-149377766-G-T is described in ClinVar as [Benign]. Clinvar id is 1295410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAB2	NM_001292034.3	c.103-252G>T		intron_variant	Intron 2 of 6	ENST00000637181.2	NP_001278963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAB2	ENST00000637181.2	c.103-252G>T		intron_variant	Intron 2 of 6	1	NM_001292034.3	ENSP00000490618.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135312 AN: 152084 Hom.: 60200 Cov.: 32

Gnomad AFR AF: 0.887

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.908

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

GnomAD4 genome AF: 0.890 AC: 135418 AN: 152202 Hom.: 60250 Cov.: 32 AF XY: 0.889 AC XY: 66183 AN XY: 74406

African (AFR) AF: 0.887 AC: 36840 AN: 41510

American (AMR) AF: 0.898 AC: 13739 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3262 AN: 3470

East Asian (EAS) AF: 0.887 AC: 4597 AN: 5182

South Asian (SAS) AF: 0.913 AC: 4408 AN: 4828

European-Finnish (FIN) AF: 0.872 AC: 9231 AN: 10590

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60389 AN: 68010

Other (OTH) AF: 0.909 AC: 1917 AN: 2110

Alfa AF: 0.880 Hom.: 3120

Bravo AF: 0.893

Asia WGS AF: 0.887 AC: 3072 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.30
DANN	Benign	0.19
PhyloP100		-0.27
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: rs6916134; hg19: chr6-149698902;