6-32828703-T-C

Variant names:

• chr6-32828703-T-C
• rs241451
• NM_001290043.2:c.*203A>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.*203A>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 0.424 in 692,078 control chromosomes in the GnomAD database, including 44,773 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 0.34 (7448 hom., cov: 21)
  • Exomes 𝑓: 0.44 (37325 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26
• Publications: 37 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 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.*203A>G		3_prime_UTR	Exon 12 of 12	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1932+697A>G		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.*203A>G		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+697A>G		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698449.1		c.*203A>G		3_prime_UTR	Exon 13 of 13	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes AF: 0.344 AC: 45533 AN: 132364 Hom.: 7441 Cov.: 21

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.442 AC: 247577 AN: 559640 Hom.: 37325 Cov.: 10 AF XY: 0.440 AC XY: 114710 AN XY: 260530

African (AFR) AF: 0.394 AC: 4702 AN: 11946

American (AMR) AF: 0.218 AC: 965 AN: 4436

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 2010 AN: 4276

East Asian (EAS) AF: 0.356 AC: 1922 AN: 5398

South Asian (SAS) AF: 0.442 AC: 7487 AN: 16922

European-Finnish (FIN) AF: 0.251 AC: 252 AN: 1002

Middle Eastern (MID) AF: 0.435 AC: 501 AN: 1152

European-Non Finnish (NFE) AF: 0.447 AC: 221343 AN: 495328

Other (OTH) AF: 0.438 AC: 8395 AN: 19180

GnomAD4 genome AF: 0.344 AC: 45564 AN: 132438 Hom.: 7448 Cov.: 21 AF XY: 0.354 AC XY: 22458 AN XY: 63408

African (AFR) AF: 0.300 AC: 10368 AN: 34516

American (AMR) AF: 0.386 AC: 4999 AN: 12960

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1257 AN: 3294

East Asian (EAS) AF: 0.426 AC: 1823 AN: 4278

South Asian (SAS) AF: 0.442 AC: 1769 AN: 4000

European-Finnish (FIN) AF: 0.479 AC: 3753 AN: 7836

Middle Eastern (MID) AF: 0.351 AC: 97 AN: 276

European-Non Finnish (NFE) AF: 0.327 AC: 20489 AN: 62616

Other (OTH) AF: 0.344 AC: 620 AN: 1800

Alfa AF: 0.318 Hom.: 31544

Bravo AF: 0.320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.45
PhyloP100		-3.3
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: rs241451; hg19: chr6-32796480; COSMIC: COSV66500441; COSMIC: COSV66500441;