6-32829584-C-T

Variant names:

• chr6-32829584-C-T
• rs241440
• NM_001290043.2:c.1796-48G>A

Variant summary

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

The NM_001290043.2(TAP2):​c.1796-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,610,984 control chromosomes in the GnomAD database, including 60,405 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 (5342 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55063 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 47 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=-0.82).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.1796-48G>A		intron	N/A	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1796-48G>A		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.1796-48G>A		intron	N/A	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1796-48G>A		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698449.1		c.1829-48G>A		intron	N/A	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38486 AN: 152000 Hom.: 5331 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.275

GnomAD2 exomes AF: 0.298 AC: 73845 AN: 248190 AF XY: 0.301

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.356

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.284

GnomAD4 exome AF: 0.269 AC: 391934 AN: 1458866 Hom.: 55063 Cov.: 34 AF XY: 0.272 AC XY: 197630 AN XY: 725678

African (AFR) AF: 0.152 AC: 5095 AN: 33458

American (AMR) AF: 0.339 AC: 15076 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 9122 AN: 26098

East Asian (EAS) AF: 0.350 AC: 13889 AN: 39660

South Asian (SAS) AF: 0.394 AC: 33876 AN: 86024

European-Finnish (FIN) AF: 0.339 AC: 17678 AN: 52142

Middle Eastern (MID) AF: 0.287 AC: 1651 AN: 5754

European-Non Finnish (NFE) AF: 0.251 AC: 278934 AN: 1110900

Other (OTH) AF: 0.275 AC: 16613 AN: 60324

GnomAD4 genome AF: 0.253 AC: 38516 AN: 152118 Hom.: 5342 Cov.: 32 AF XY: 0.262 AC XY: 19481 AN XY: 74376

African (AFR) AF: 0.152 AC: 6294 AN: 41508

American (AMR) AF: 0.316 AC: 4836 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1845 AN: 5160

South Asian (SAS) AF: 0.399 AC: 1925 AN: 4822

European-Finnish (FIN) AF: 0.344 AC: 3640 AN: 10568

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

European-Non Finnish (NFE) AF: 0.261 AC: 17766 AN: 67976

Other (OTH) AF: 0.275 AC: 581 AN: 2110

Alfa AF: 0.253 Hom.: 15840

Bravo AF: 0.245

Asia WGS AF: 0.360 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.64
PhyloP100		0.49
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: rs241440; hg19: chr6-32797361; COSMIC: COSV66500261; COSMIC: COSV66500261;