6-32828367-A-G

Variant names:

• chr6-32828367-A-G
• rs241454
• NM_001290043.2:c.*539T>C

Variant summary

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

The NM_001290043.2(TAP2):​c.*539T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 985,118 control chromosomes in the GnomAD database, including 32,331 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 (5627 hom., cov: 31)
  • Exomes 𝑓: 0.25 (26704 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397
• Publications: 31 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 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.*539T>C		3_prime_UTR	Exon 12 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.1932+1033T>C		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.*539T>C		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+1033T>C		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000698440.1		c.*539T>C		3_prime_UTR	Exon 13 of 13	ENSP00000513722.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40162 AN: 151834 Hom.: 5617 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.250 AC: 208193 AN: 833166 Hom.: 26704 Cov.: 30 AF XY: 0.250 AC XY: 96107 AN XY: 384802

African (AFR) AF: 0.183 AC: 2884 AN: 15784

American (AMR) AF: 0.317 AC: 326 AN: 1030

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1791 AN: 5148

East Asian (EAS) AF: 0.352 AC: 1284 AN: 3650

South Asian (SAS) AF: 0.411 AC: 6771 AN: 16474

European-Finnish (FIN) AF: 0.337 AC: 95 AN: 282

Middle Eastern (MID) AF: 0.281 AC: 455 AN: 1620

European-Non Finnish (NFE) AF: 0.246 AC: 187399 AN: 761880

Other (OTH) AF: 0.263 AC: 7188 AN: 27298

GnomAD4 genome AF: 0.265 AC: 40195 AN: 151952 Hom.: 5627 Cov.: 31 AF XY: 0.273 AC XY: 20263 AN XY: 74258

African (AFR) AF: 0.185 AC: 7670 AN: 41438

American (AMR) AF: 0.329 AC: 5025 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3466

East Asian (EAS) AF: 0.363 AC: 1872 AN: 5154

South Asian (SAS) AF: 0.399 AC: 1915 AN: 4804

European-Finnish (FIN) AF: 0.344 AC: 3624 AN: 10536

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

European-Non Finnish (NFE) AF: 0.263 AC: 17844 AN: 67954

Other (OTH) AF: 0.289 AC: 612 AN: 2114

Alfa AF: 0.263 Hom.: 6658

Bravo AF: 0.259

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		0.40
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: rs241454; hg19: chr6-32796144;