NM_001290043.2:c.*664G>T

Variant names:

• chr6-32828242-C-A
• rs241455
• NM_001290043.2:c.*664G>T

Variant summary

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

The NM_001290043.2(TAP2):​c.*664G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 972,548 control chromosomes in the GnomAD database, including 31,368 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 (5605 hom., cov: 32)
  • Exomes 𝑓: 0.25 (25763 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 26 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 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.*664G>T		3_prime_UTR	Exon 12 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.1932+1158G>T		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.*664G>T		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+1158G>T		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000698440.1		c.*664G>T		3_prime_UTR	Exon 13 of 13	ENSP00000513722.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40086 AN: 151880 Hom.: 5595 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.246 AC: 202220 AN: 820550 Hom.: 25763 Cov.: 16 AF XY: 0.246 AC XY: 93484 AN XY: 379278

African (AFR) AF: 0.178 AC: 2780 AN: 15582

American (AMR) AF: 0.317 AC: 306 AN: 966

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1752 AN: 5070

East Asian (EAS) AF: 0.350 AC: 1241 AN: 3544

South Asian (SAS) AF: 0.408 AC: 6575 AN: 16118

European-Finnish (FIN) AF: 0.332 AC: 91 AN: 274

Middle Eastern (MID) AF: 0.279 AC: 444 AN: 1594

European-Non Finnish (NFE) AF: 0.243 AC: 182058 AN: 750542

Other (OTH) AF: 0.260 AC: 6973 AN: 26860

GnomAD4 genome AF: 0.264 AC: 40120 AN: 151998 Hom.: 5605 Cov.: 32 AF XY: 0.272 AC XY: 20233 AN XY: 74294

African (AFR) AF: 0.183 AC: 7592 AN: 41442

American (AMR) AF: 0.328 AC: 5019 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1868 AN: 5162

South Asian (SAS) AF: 0.399 AC: 1923 AN: 4814

European-Finnish (FIN) AF: 0.345 AC: 3629 AN: 10532

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

European-Non Finnish (NFE) AF: 0.262 AC: 17842 AN: 67974

Other (OTH) AF: 0.290 AC: 612 AN: 2110

Alfa AF: 0.229 Hom.: 5031

Bravo AF: 0.258

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.81
PhyloP100		-0.032
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs241455; hg19: chr6-32796019;