rs2857101

Positions:

• chr6-32826899-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290043.2(TAP2):​c.*2007A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 985,176 control chromosomes in the GnomAD database, including 31,362 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 0.25 (5205 hom., cov: 32)
  • Exomes 𝑓: 0.25 (26157 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

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 = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.*2007A>G		3_prime_UTR_variant	12/12	ENST00000374897.4
TAP2	NM_018833.3	c.1932+2501A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.*2007A>G		3_prime_UTR_variant	12/12	1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37807 AN: 152036 Hom.: 5199 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.247 AC: 205931 AN: 833022 Hom.: 26157 Cov.: 33 AF XY: 0.247 AC XY: 95062 AN XY: 384678

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.342

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.249 AC: 37829 AN: 152154 Hom.: 5205 Cov.: 32 AF XY: 0.257 AC XY: 19140 AN XY: 74384

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.269

Alfa AF: 0.268 Hom.: 8399

Bravo AF: 0.241

Asia WGS AF: 0.342 AC: 1190 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	5.7
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs2857101; hg19: chr6-32794676;