rs17034

Variant names:

• chr6-32828744-C-T
• rs17034
• NM_001290043.2:c.*162G>A

Variant summary

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

The NM_001290043.2(TAP2):​c.*162G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,141,594 control chromosomes in the GnomAD database, including 38,526 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 0.26 (5327 hom., cov: 26)
  • Exomes 𝑓: 0.26 (33199 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 36 publications found

Genes affected

TAP2 (HGNC:44): (transporter 2, ATP binding cassette subfamily B member) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. This gene is located 7 kb telomeric to gene family member ABCB2. The protein encoded by this gene is involved in antigen presentation. This protein forms a heterodimer with ABCB2 in order to transport peptides from the cytoplasm to the endoplasmic reticulum. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Alternative splicing of this gene produces products which differ in peptide selectivity and level of restoration of surface expression of MHC class I molecules. [provided by RefSeq, Feb 2014]

TAP2 Gene-Disease associations (from GenCC):

• MHC class I deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250264 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290043.2. 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
	TAP2	NM_001290043.2	MANE Select	c.*162G>A		3_prime_UTR	Exon 12 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.1932+656G>A		intron	N/A	NP_061313.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.*162G>A		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+656G>A		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000485701.2	TSL:3	n.6152G>A		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.259 AC: 38566 AN: 148984 Hom.: 5322 Cov.: 26

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.280

GnomAD4 exome AF: 0.256 AC: 253898 AN: 992496 Hom.: 33199 Cov.: 34 AF XY: 0.257 AC XY: 120571 AN XY: 469400

African (AFR) AF: 0.177 AC: 3819 AN: 21584

American (AMR) AF: 0.322 AC: 4085 AN: 12698

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 3441 AN: 9752

East Asian (EAS) AF: 0.379 AC: 6528 AN: 17238

South Asian (SAS) AF: 0.366 AC: 12245 AN: 33448

European-Finnish (FIN) AF: 0.382 AC: 3052 AN: 7998

Middle Eastern (MID) AF: 0.282 AC: 650 AN: 2302

European-Non Finnish (NFE) AF: 0.247 AC: 210159 AN: 851346

Other (OTH) AF: 0.275 AC: 9919 AN: 36130

GnomAD4 genome AF: 0.259 AC: 38588 AN: 149098 Hom.: 5327 Cov.: 26 AF XY: 0.266 AC XY: 19333 AN XY: 72604

African (AFR) AF: 0.173 AC: 7015 AN: 40486

American (AMR) AF: 0.319 AC: 4770 AN: 14954

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1176 AN: 3454

East Asian (EAS) AF: 0.362 AC: 1791 AN: 4946

South Asian (SAS) AF: 0.397 AC: 1848 AN: 4658

European-Finnish (FIN) AF: 0.343 AC: 3437 AN: 10022

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

European-Non Finnish (NFE) AF: 0.260 AC: 17540 AN: 67342

Other (OTH) AF: 0.280 AC: 574 AN: 2048

Alfa AF: 0.250 Hom.: 7610

Bravo AF: 0.254

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.68
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17034; hg19: chr6-32796521; COSMIC: COSV66500449; COSMIC: COSV66500449;