6-32828449-G-A

Variant names:

• chr6-32828449-G-A
• rs241453
• NM_001290043.2:c.*457C>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.*457C>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 984,080 control chromosomes in the GnomAD database, including 31,745 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 (5318 hom., cov: 32)
  • Exomes 𝑓: 0.25 (26427 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260
• Publications: 48 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.*457C>T		3_prime_UTR	Exon 12 of 12	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1932+951C>T		intron	N/A	NP_061313.2	Q9UP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.*457C>T		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+951C>T		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698440.1		c.*457C>T		3_prime_UTR	Exon 13 of 13	ENSP00000513722.1	Q03519-1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38391 AN: 151892 Hom.: 5308 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.248 AC: 206684 AN: 832070 Hom.: 26427 Cov.: 22 AF XY: 0.248 AC XY: 95463 AN XY: 384364

African (AFR) AF: 0.146 AC: 2309 AN: 15766

American (AMR) AF: 0.300 AC: 325 AN: 1084

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1789 AN: 5138

East Asian (EAS) AF: 0.346 AC: 1271 AN: 3676

South Asian (SAS) AF: 0.403 AC: 6634 AN: 16442

European-Finnish (FIN) AF: 0.339 AC: 95 AN: 280

Middle Eastern (MID) AF: 0.275 AC: 444 AN: 1612

European-Non Finnish (NFE) AF: 0.246 AC: 186790 AN: 760802

Other (OTH) AF: 0.258 AC: 7027 AN: 27270

GnomAD4 genome AF: 0.253 AC: 38424 AN: 152010 Hom.: 5318 Cov.: 32 AF XY: 0.262 AC XY: 19441 AN XY: 74272

African (AFR) AF: 0.148 AC: 6130 AN: 41472

American (AMR) AF: 0.323 AC: 4931 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3466

East Asian (EAS) AF: 0.358 AC: 1850 AN: 5172

South Asian (SAS) AF: 0.384 AC: 1849 AN: 4818

European-Finnish (FIN) AF: 0.345 AC: 3642 AN: 10542

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17814 AN: 67970

Other (OTH) AF: 0.276 AC: 580 AN: 2104

Alfa AF: 0.259 Hom.: 22287

Bravo AF: 0.245

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.47
PhyloP100		0.026
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: rs241453; hg19: chr6-32796226;