rs4148876

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001290043.2(TAP2):c.1951C>T(p.Arg651Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 1,549,556 control chromosomes in the GnomAD database, including 4,055 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R651H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.058 ( 318 hom., cov: 31)

Exomes 𝑓: 0.070 ( 3737 hom. )

Consequence

TAP2
NM_001290043.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.818

Publications

77 publications found

Variant links:

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

TAP2 links:

ENSG00000250264 (HGNC:):

ENSG00000250264 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017689466).

BP6

Variant 6-32829016-G-A is Benign according to our data. Variant chr6-32829016-G-A is described in ClinVar as Benign. ClinVar VariationId is 1164495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1951C>T	p.Arg651Cys	missense_variant	Exon 12 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1932+384C>T		intron_variant	Intron 11 of 11		NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1951C>T	p.Arg651Cys	missense_variant	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1932+384C>T		intron_variant	Intron 11 of 14	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8824

AN:

152136

Hom.:

316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0151

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0817

Gnomad ASJ

AF:

0.129

Gnomad EAS

AF:

0.0738

Gnomad SAS

AF:

0.0520

Gnomad FIN

AF:

0.0740

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0722

Gnomad OTH

AF:

0.0516

GnomAD2 exomes

AF:

0.0764

AC:

11720

AN:

153326

AF XY:

0.0733

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.0768

Gnomad FIN exome

AF:

0.0730

Gnomad NFE exome

AF:

0.0702

Gnomad OTH exome

AF:

0.0694

GnomAD4 exome

AF:

0.0702

AC:

98067

AN:

1397302

Hom.:

3737

Cov.:

AF XY:

0.0695

AC XY:

47910

AN XY:

689074

show subpopulations

African (AFR)

AF:

0.0117

AC:

372

AN:

31706

American (AMR)

AF:

0.108

AC:

3908

AN:

36088

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

2930

AN:

25258

East Asian (EAS)

AF:

0.120

AC:

4284

AN:

35794

South Asian (SAS)

AF:

0.0554

AC:

4392

AN:

79330

European-Finnish (FIN)

AF:

0.0736

AC:

3446

AN:

46830

Middle Eastern (MID)

AF:

0.0602

AC:

343

AN:

5694

European-Non Finnish (NFE)

AF:

0.0691

AC:

74506

AN:

1078616

Other (OTH)

AF:

0.0670

AC:

3886

AN:

57986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

5594

11188

16781

22375

27969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2858

5716

8574

11432

14290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0580

AC:

8829

AN:

152254

Hom.:

318

Cov.:

AF XY:

0.0581

AC XY:

4326

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0150

AC:

623

AN:

41540

American (AMR)

AF:

0.0820

AC:

1255

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

449

AN:

3468

East Asian (EAS)

AF:

0.0740

AC:

384

AN:

5190

South Asian (SAS)

AF:

0.0527

AC:

254

AN:

4824

European-Finnish (FIN)

AF:

0.0740

AC:

784

AN:

10596

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0722

AC:

4913

AN:

68014

Other (OTH)

AF:

0.0506

AC:

107

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

425

850

1275

1700

2125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0740

Hom.:

1130

Bravo

AF:

0.0580

TwinsUK

AF:

0.0739

AC:

274

ALSPAC

AF:

0.0688

AC:

265

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.0542

AC:

259

ExAC

AF:

0.0351

AC:

3393

Asia WGS

AF:

0.0580

AC:

202

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.055

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.7

.;L

PhyloP100

0.82

PrimateAI

Benign

0.30

PROVEAN

Benign

0.21

.;N

REVEL

Uncertain

0.29

Sift

Benign

0.19

.;T

Sift4G

Benign

0.20

T;T

Polyphen

1.0

.;D

Vest4

0.076

ClinPred

0.0067

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.085

gMVP

0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over