6-32822282-T-C

Variant names:

• chr6-32822282-T-C
• rs2857105
• ENST00000452392.2:c.1933-5330A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_018833.3(TAP2):​c.*7A>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 0.0345 in 1,550,926 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.037 (138 hom., cov: 32)
  • Exomes 𝑓: 0.034 (984 hom.)
• Consequence: TAP2 NM_018833.3 3_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.519
• Publications: 20 publications found

Genes affected

ENSG00000250264 (HGNC:):

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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-32822282-T-C is Benign according to our data. Variant chr6-32822282-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060503.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018833.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_018833.3		c.*7A>G		3_prime_UTR	Exon 12 of 12	NP_061313.2	Q9UP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1933-5330A>G		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000652259.1		c.*7A>G		3_prime_UTR	Exon 12 of 12	ENSP00000498827.1	Q03519-2
	ENSG00000307274	ENST00000824890.1		n.79+1402T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5690 AN: 152048 Hom.: 136 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0446

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00321

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.0598

GnomAD2 exomes AF: 0.0281 AC: 5877 AN: 209392 AF XY: 0.0271

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.0407

Gnomad ASJ exome AF: 0.0441

Gnomad EAS exome AF: 0.00127

Gnomad FIN exome AF: 0.00236

Gnomad NFE exome AF: 0.0356

Gnomad OTH exome AF: 0.0449

GnomAD4 exome AF: 0.0342 AC: 47786 AN: 1398762 Hom.: 984 Cov.: 27 AF XY: 0.0331 AC XY: 23009 AN XY: 695250

African (AFR) AF: 0.0446 AC: 1413 AN: 31710

American (AMR) AF: 0.0452 AC: 1876 AN: 41536

Ashkenazi Jewish (ASJ) AF: 0.0441 AC: 1116 AN: 25288

East Asian (EAS) AF: 0.000713 AC: 28 AN: 39272

South Asian (SAS) AF: 0.00467 AC: 378 AN: 81020

European-Finnish (FIN) AF: 0.00370 AC: 188 AN: 50834

Middle Eastern (MID) AF: 0.0213 AC: 120 AN: 5626

European-Non Finnish (NFE) AF: 0.0383 AC: 40807 AN: 1065448

Other (OTH) AF: 0.0321 AC: 1860 AN: 58028

GnomAD4 genome AF: 0.0374 AC: 5691 AN: 152164 Hom.: 138 Cov.: 32 AF XY: 0.0354 AC XY: 2632 AN XY: 74386

African (AFR) AF: 0.0461 AC: 1914 AN: 41498

American (AMR) AF: 0.0561 AC: 857 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 155 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5188

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4820

European-Finnish (FIN) AF: 0.00321 AC: 34 AN: 10576

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0375 AC: 2550 AN: 68008

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0382 Hom.: 447

Bravo AF: 0.0446

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TAP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.72
PhyloP100		0.52
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: rs2857105; hg19: chr6-32790059;