6-32829532-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001290043.2(TAP2):c.1800A>C(p.Val600Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 1,613,994 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 387 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2070 hom. )

Consequence

TAP2
NM_001290043.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.01

Publications

8 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
MHC class I deficiency 1
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 6-32829532-T-G is Benign according to our data. Variant chr6-32829532-T-G is described in ClinVar as Benign. ClinVar VariationId is 403514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.1800A>C	p.Val600Val	synonymous	Exon 11 of 12	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1800A>C	p.Val600Val	synonymous	Exon 11 of 12	NP_061313.2	Q9UP03

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAP2	ENST00000374897.4	TSL:1 MANE Select	c.1800A>C	p.Val600Val	synonymous	Exon 11 of 12	ENSP00000364032.3	Q03519-1
ENSG00000250264	ENST00000452392.2	TSL:2	c.1800A>C	p.Val600Val	synonymous	Exon 11 of 15	ENSP00000391806.2	E7ENX8
TAP2	ENST00000698449.1		c.1833A>C	p.Val611Val	synonymous	Exon 12 of 13	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9766

AN:

152078

Hom.:

387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0395

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0397

GnomAD2 exomes

AF:

0.0510

AC:

12810

AN:

251306

AF XY:

0.0497

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0268

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.0319

Gnomad FIN exome

AF:

0.0987

Gnomad NFE exome

AF:

0.0575

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0494

AC:

72185

AN:

1461798

Hom.:

2070

Cov.:

AF XY:

0.0483

AC XY:

35119

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.104

AC:

3473

AN:

33480

American (AMR)

AF:

0.0283

AC:

1265

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0295

AC:

771

AN:

26130

East Asian (EAS)

AF:

0.0468

AC:

1856

AN:

39700

South Asian (SAS)

AF:

0.0119

AC:

1029

AN:

86248

European-Finnish (FIN)

AF:

0.0981

AC:

5237

AN:

53398

Middle Eastern (MID)

AF:

0.0258

AC:

149

AN:

5768

European-Non Finnish (NFE)

AF:

0.0502

AC:

55787

AN:

1111968

Other (OTH)

AF:

0.0433

AC:

2618

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

3988

7975

11963

15950

19938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2022

4044

6066

8088

10110

<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:

0.0642

AC:

9769

AN:

152196

Hom.:

387

Cov.:

AF XY:

0.0654

AC XY:

4863

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0997

AC:

4140

AN:

41508

American (AMR)

AF:

0.0394

AC:

603

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3472

East Asian (EAS)

AF:

0.0350

AC:

181

AN:

5176

South Asian (SAS)

AF:

0.0120

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.101

AC:

1072

AN:

10594

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0508

AC:

3456

AN:

68004

Other (OTH)

AF:

0.0426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

474

948

1422

1896

2370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0534

Hom.:

437

Bravo

AF:

0.0612

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0510

EpiControl

AF:

0.0501

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

MHC class I deficiency (1)

not specified (1)

TAP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.18

(source)

DANN

Benign

0.61

PhyloP100

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over