rs28724898

Variant names:

• chr6-32835631-T-A
• rs28724898
• NM_001290043.2:c.739+12A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001290043.2(TAP2):​c.739+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,612,946 control chromosomes in the GnomAD database, including 1,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (251 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1330 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.190
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-32835631-T-A is Benign according to our data. Variant chr6-32835631-T-A is described in ClinVar as Benign. ClinVar VariationId is 403517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0844 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.739+12A>T		intron	N/A	NP_001276972.1
	TAP2	NM_018833.3		c.739+12A>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.739+12A>T		intron	N/A	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.739+12A>T		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.739+12A>T		intron	N/A	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7628 AN: 152092 Hom.: 250 Cov.: 31

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0407

GnomAD2 exomes AF: 0.0375 AC: 9254 AN: 246556 AF XY: 0.0394

Gnomad AFR exome AF: 0.0888

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0394

Gnomad EAS exome AF: 0.0189

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0339

GnomAD4 exome AF: 0.0384 AC: 56027 AN: 1460736 Hom.: 1330 Cov.: 33 AF XY: 0.0390 AC XY: 28312 AN XY: 726686

African (AFR) AF: 0.0907 AC: 3037 AN: 33480

American (AMR) AF: 0.0254 AC: 1138 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0393 AC: 1027 AN: 26136

East Asian (EAS) AF: 0.00904 AC: 359 AN: 39700

South Asian (SAS) AF: 0.0646 AC: 5576 AN: 86258

European-Finnish (FIN) AF: 0.0112 AC: 588 AN: 52318

Middle Eastern (MID) AF: 0.0359 AC: 207 AN: 5766

European-Non Finnish (NFE) AF: 0.0373 AC: 41529 AN: 1111972

Other (OTH) AF: 0.0425 AC: 2566 AN: 60382

GnomAD4 genome AF: 0.0502 AC: 7639 AN: 152210 Hom.: 251 Cov.: 31 AF XY: 0.0487 AC XY: 3626 AN XY: 74426

African (AFR) AF: 0.0867 AC: 3599 AN: 41500

American (AMR) AF: 0.0360 AC: 551 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5186

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4828

European-Finnish (FIN) AF: 0.00895 AC: 95 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0373 AC: 2537 AN: 68010

Other (OTH) AF: 0.0398 AC: 84 AN: 2108

Alfa AF: 0.0423 Hom.: 26

Bravo AF: 0.0515

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

MHC class I deficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Sep 08, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.61
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs28724898; hg19: chr6-32803408;