6-32828569-T-C

Variant names:

• chr6-32828569-T-C
• rs241452
• NM_001290043.2:c.*337A>G

Variant summary

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

The NM_001290043.2(TAP2):​c.*337A>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 0.251 in 1,012,504 control chromosomes in the GnomAD database, including 33,035 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 (5645 hom., cov: 31)
  • Exomes 𝑓: 0.25 (27390 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 33 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.*337A>G		3_prime_UTR_variant	Exon 12 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1932+831A>G		intron_variant	Intron 11 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.*337A>G		3_prime_UTR_variant	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1932+831A>G		intron_variant	Intron 11 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40226 AN: 151972 Hom.: 5635 Cov.: 31

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.248 AC: 213490 AN: 860414 Hom.: 27390 Cov.: 20 AF XY: 0.248 AC XY: 99113 AN XY: 399450

African (AFR) AF: 0.178 AC: 3016 AN: 16974

American (AMR) AF: 0.288 AC: 1198 AN: 4162

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 2063 AN: 6124

East Asian (EAS) AF: 0.339 AC: 2360 AN: 6958

South Asian (SAS) AF: 0.399 AC: 7322 AN: 18364

European-Finnish (FIN) AF: 0.269 AC: 307 AN: 1142

Middle Eastern (MID) AF: 0.280 AC: 487 AN: 1738

European-Non Finnish (NFE) AF: 0.244 AC: 189108 AN: 775992

Other (OTH) AF: 0.263 AC: 7629 AN: 28960

GnomAD4 genome AF: 0.265 AC: 40258 AN: 152090 Hom.: 5645 Cov.: 31 AF XY: 0.273 AC XY: 20298 AN XY: 74336

African (AFR) AF: 0.185 AC: 7674 AN: 41482

American (AMR) AF: 0.329 AC: 5031 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1893 AN: 5182

South Asian (SAS) AF: 0.398 AC: 1917 AN: 4814

European-Finnish (FIN) AF: 0.345 AC: 3646 AN: 10570

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

European-Non Finnish (NFE) AF: 0.263 AC: 17846 AN: 67968

Other (OTH) AF: 0.292 AC: 617 AN: 2116

Alfa AF: 0.257 Hom.: 13868

Bravo AF: 0.259

Asia WGS AF: 0.365 AC: 1267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-0.021
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: rs241452; hg19: chr6-32796346;