rs241448

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_001290043.2(TAP2):c.2059T>C(p.Ter687Glnext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,543,082 control chromosomes in the GnomAD database, including 58,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.27 ( 5925 hom., cov: 30)

Exomes 𝑓: 0.27 ( 52954 hom. )

Consequence

TAP2
NM_001290043.2 stop_lost

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.36

Publications

81 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 -14 ACMG points.

PM4

Stoplost variant in NM_001290043.2 Downstream stopcodon found after 34 codons.

BP6

Variant 6-32828908-A-G is Benign according to our data. Variant chr6-32828908-A-G is described in ClinVar as Benign. ClinVar VariationId is 403510.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.2059T>C	p.Ter687Glnext*?	stop_lost	Exon 12 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1932+492T>C		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.2059T>C	p.Ter687Glnext*?	stop_lost	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1932+492T>C		intron_variant	Intron 11 of 14	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41592

AN:

151740

Hom.:

5915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.296

GnomAD2 exomes

AF:

0.316

AC:

47140

AN:

148998

AF XY:

0.318

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.270

AC:

376064

AN:

1391224

Hom.:

52954

Cov.:

AF XY:

0.274

AC XY:

187494

AN XY:

685394

show subpopulations

African (AFR)

AF:

0.218

AC:

6892

AN:

31566

American (AMR)

AF:

0.349

AC:

12483

AN:

35728

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

8784

AN:

25172

East Asian (EAS)

AF:

0.354

AC:

12598

AN:

35636

South Asian (SAS)

AF:

0.393

AC:

30817

AN:

78388

European-Finnish (FIN)

AF:

0.335

AC:

15387

AN:

45872

Middle Eastern (MID)

AF:

0.298

AC:

1675

AN:

5624

European-Non Finnish (NFE)

AF:

0.252

AC:

271164

AN:

1075496

Other (OTH)

AF:

0.282

AC:

16264

AN:

57742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

15237

30474

45710

60947

76184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9350

18700

28050

37400

46750

<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:

0.274

AC:

41625

AN:

151858

Hom.:

5925

Cov.:

AF XY:

0.282

AC XY:

20934

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.217

AC:

8974

AN:

41404

American (AMR)

AF:

0.334

AC:

5101

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1195

AN:

3470

East Asian (EAS)

AF:

0.367

AC:

1884

AN:

5140

South Asian (SAS)

AF:

0.399

AC:

1916

AN:

4806

European-Finnish (FIN)

AF:

0.345

AC:

3634

AN:

10544

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.263

AC:

17856

AN:

67892

Other (OTH)

AF:

0.296

AC:

625

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1518

3037

4555

6074

7592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.274

Hom.:

13234

Bravo

AF:

0.270

TwinsUK

AF:

0.225

AC:

833

ALSPAC

AF:

0.238

AC:

919

ESP6500AA

AF:

0.161

AC:

385

ESP6500EA

AF:

0.190

AC:

895

ExAC

AF:

0.145

AC:

11752

Asia WGS

AF:

0.366

AC:

1274

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

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.019

(source)

DANN

Benign

0.32

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.014

PhyloP100

-1.4

GERP RS

-12

Mutation Taster

=160/40

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