chr6-32829391-G-A

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.1932+9C>T 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 1,586,668 control chromosomes in the GnomAD database, including 58,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5465 hom., cov: 31)

Exomes 𝑓: 0.27 ( 53416 hom. )

Consequence

TAP2
NM_001290043.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.878

Publications

17 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 (BayesDel_noAF=-0.81).

BP6

Variant 6-32829391-G-A is Benign according to our data. Variant chr6-32829391-G-A is described in ClinVar as Benign. ClinVar VariationId is 403512.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.1932+9C>T		intron_variant	Intron 11 of 11	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1932+9C>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.1932+9C>T		intron_variant	Intron 11 of 11	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1932+9C>T		intron_variant	Intron 11 of 14	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39662

AN:

151882

Hom.:

5455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.359

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.289

AC:

60170

AN:

208310

AF XY:

0.294

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.351

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.252

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.267

AC:

383734

AN:

1434668

Hom.:

53416

Cov.:

AF XY:

0.271

AC XY:

192733

AN XY:

710992

show subpopulations

African (AFR)

AF:

0.182

AC:

6011

AN:

33100

American (AMR)

AF:

0.284

AC:

11423

AN:

40176

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

8907

AN:

25526

East Asian (EAS)

AF:

0.350

AC:

13545

AN:

38716

South Asian (SAS)

AF:

0.391

AC:

32347

AN:

82832

European-Finnish (FIN)

AF:

0.337

AC:

17386

AN:

51538

Middle Eastern (MID)

AF:

0.292

AC:

1606

AN:

5504

European-Non Finnish (NFE)

AF:

0.251

AC:

275992

AN:

1097846

Other (OTH)

AF:

0.278

AC:

16517

AN:

59430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

15617

31234

46851

62468

78085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9424

18848

28272

37696

47120

<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:

0.261

AC:

39693

AN:

152000

Hom.:

5465

Cov.:

AF XY:

0.269

AC XY:

19995

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.183

AC:

7571

AN:

41474

American (AMR)

AF:

0.306

AC:

4678

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1192

AN:

3470

East Asian (EAS)

AF:

0.358

AC:

1837

AN:

5128

South Asian (SAS)

AF:

0.398

AC:

1920

AN:

4820

European-Finnish (FIN)

AF:

0.344

AC:

3636

AN:

10560

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17813

AN:

67950

Other (OTH)

AF:

0.287

AC:

607

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1452

2904

4355

5807

7259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.248

Hom.:

9772

Bravo

AF:

0.253

Asia WGS

AF:

0.363

AC:

1262

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.14

(source)

DANN

Benign

0.59

PhyloP100

-0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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