rs241447

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1993A>G(p.Thr665Ala) variant causes a missense change. The variant allele was found at a frequency of 0.269 in 1,549,446 control chromosomes in the GnomAD database, including 58,603 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5642 hom., cov: 30)

Exomes 𝑓: 0.27 ( 52961 hom. )

Consequence

TAP2
NM_001290043.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.70

Publications

103 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=0.031624883).

BP6

Variant 6-32828974-T-C is Benign according to our data. Variant chr6-32828974-T-C is described in ClinVar as Benign. ClinVar VariationId is 403511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1993A>G	p.Thr665Ala	missense_variant	Exon 12 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1932+426A>G		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.1993A>G	p.Thr665Ala	missense_variant	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1932+426A>G		intron_variant	Intron 11 of 14	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40167

AN:

151784

Hom.:

5632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.291

GnomAD2 exomes

AF:

0.313

AC:

47971

AN:

153132

AF XY:

0.315

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.355

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.359

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.298

GnomAD4 exome

AF:

0.269

AC:

376632

AN:

1397544

Hom.:

52961

Cov.:

AF XY:

0.273

AC XY:

188203

AN XY:

689444

show subpopulations

African (AFR)

AF:

0.184

AC:

5844

AN:

31716

American (AMR)

AF:

0.347

AC:

12518

AN:

36028

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

8834

AN:

25274

East Asian (EAS)

AF:

0.353

AC:

12682

AN:

35886

South Asian (SAS)

AF:

0.393

AC:

31012

AN:

78988

European-Finnish (FIN)

AF:

0.335

AC:

15679

AN:

46812

Middle Eastern (MID)

AF:

0.297

AC:

1692

AN:

5694

European-Non Finnish (NFE)

AF:

0.252

AC:

272114

AN:

1079122

Other (OTH)

AF:

0.280

AC:

16257

AN:

58024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

15886

31772

47658

63544

79430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9334

18668

28002

37336

46670

<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:

0.265

AC:

40199

AN:

151902

Hom.:

5642

Cov.:

AF XY:

0.273

AC XY:

20265

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.185

AC:

7661

AN:

41426

American (AMR)

AF:

0.329

AC:

5028

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1194

AN:

3470

East Asian (EAS)

AF:

0.366

AC:

1886

AN:

5160

South Asian (SAS)

AF:

0.399

AC:

1913

AN:

4800

European-Finnish (FIN)

AF:

0.345

AC:

3631

AN:

10530

Middle Eastern (MID)

AF:

0.298

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.262

AC:

17829

AN:

67930

Other (OTH)

AF:

0.292

AC:

616

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1454

2908

4361

5815

7269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.262

Hom.:

17280

Bravo

AF:

0.259

TwinsUK

AF:

0.230

AC:

851

ALSPAC

AF:

0.239

AC:

921

ESP6500AA

AF:

0.156

AC:

397

ESP6500EA

AF:

0.214

AC:

1026

ExAC

AF:

0.190

AC:

17273

Asia WGS

AF:

0.365

AC:

1269

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:2

May 28, 2019

Mendelics

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

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.38

.;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.95

MetaRNN

Benign

0.032

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

.;L

PhyloP100

4.7

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.4

.;D

REVEL

Benign

0.29

Sift

Benign

0.037

.;D

Sift4G

Uncertain

0.010

D;D

Polyphen

0.19

.;B

Vest4

0.082

ClinPred

0.042

GERP RS

3.4

Varity_R

0.067

gMVP

0.48

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

Publications

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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