rs2272901

Variant names:

• chr6-149218637-G-A
• rs2272901
• ENST00000451095.5:n.174G>A

Variant summary

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

The ENST00000451095.5(ENSG00000228408):​n.174G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 395,378 control chromosomes in the GnomAD database, including 13,419 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 0.22 (4232 hom., cov: 32)
  • Exomes 𝑓: 0.27 (9187 hom.)
• Consequence: ENSG00000228408 ENST00000451095.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.785
• Publications: 6 publications found

Genes affected

ENSG00000228408 (HGNC:):

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451095.5. 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	NR_125861.2		n.174G>A		non_coding_transcript_exon	Exon 2 of 3
	TAB2	NM_001292035.3		c.-134G>A		5_prime_UTR	Exon 2 of 7	NP_001278964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000228408	ENST00000451095.5	TSL:1	n.174G>A		non_coding_transcript_exon	Exon 2 of 3
	ENSG00000228408	ENST00000443992.1	TSL:2	n.99G>A		non_coding_transcript_exon	Exon 2 of 3
	ENSG00000228408	ENST00000635954.1	TSL:5	n.164G>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34001 AN: 152046 Hom.: 4235 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.266 AC: 64732 AN: 243214 Hom.: 9187 Cov.: 0 AF XY: 0.270 AC XY: 37125 AN XY: 137332

African (AFR) AF: 0.126 AC: 894 AN: 7068

American (AMR) AF: 0.166 AC: 3593 AN: 21584

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 2541 AN: 7124

East Asian (EAS) AF: 0.415 AC: 3593 AN: 8656

South Asian (SAS) AF: 0.288 AC: 14147 AN: 49042

European-Finnish (FIN) AF: 0.191 AC: 1855 AN: 9712

Middle Eastern (MID) AF: 0.284 AC: 705 AN: 2486

European-Non Finnish (NFE) AF: 0.272 AC: 34344 AN: 126058

Other (OTH) AF: 0.266 AC: 3060 AN: 11484

GnomAD4 genome AF: 0.223 AC: 33994 AN: 152164 Hom.: 4232 Cov.: 32 AF XY: 0.221 AC XY: 16428 AN XY: 74390

African (AFR) AF: 0.126 AC: 5247 AN: 41512

American (AMR) AF: 0.197 AC: 3011 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2089 AN: 5160

South Asian (SAS) AF: 0.283 AC: 1362 AN: 4820

European-Finnish (FIN) AF: 0.172 AC: 1826 AN: 10592

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18334 AN: 67998

Other (OTH) AF: 0.239 AC: 504 AN: 2108

Alfa AF: 0.261 Hom.: 8463

Bravo AF: 0.221

Asia WGS AF: 0.290 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.57
PhyloP100		0.79
PromoterAI		-0.026	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2272901; hg19: chr6-149539773;