rs17034

Positions:

• chr6-32828744-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.*162G>A		3_prime_UTR_variant	12/12	ENST00000374897.4
TAP2	NM_018833.3	c.1932+656G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.*162G>A		3_prime_UTR_variant	12/12	1	NM_001290043.2	A2

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

Gnomad4 AFR exome AF: 0.177

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.275

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

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.280

Alfa AF: 0.265 Hom.: 4064

Bravo AF: 0.254

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs17034; hg19: chr6-32796521; COSMIC: COSV66500449; COSMIC: COSV66500449;