rs1042116

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.1308C>T(p.Asn436Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,612,240 control chromosomes in the GnomAD database, including 9,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 691 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8423 hom. )

Consequence

TAP2
NM_001290043.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.10

Publications

16 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

new If you want to explore the variant's impact on the transcript NM_001290043.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.62).

BP6

Variant 6-32830771-G-A is Benign according to our data. Variant chr6-32830771-G-A is described in ClinVar as Benign. ClinVar VariationId is 403516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 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.1308C>T	p.Asn436Asn	synonymous	Exon 8 of 12	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1308C>T	p.Asn436Asn	synonymous	Exon 8 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.1308C>T	p.Asn436Asn	synonymous	Exon 8 of 12	ENSP00000364032.3	Q03519-1
ENSG00000250264	ENST00000452392.2	TSL:2	c.1308C>T	p.Asn436Asn	synonymous	Exon 8 of 15	ENSP00000391806.2	E7ENX8
TAP2	ENST00000698449.1		c.1341C>T	p.Asn447Asn	synonymous	Exon 9 of 13	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes

AF:

0.0804

AC:

12225

AN:

152024

Hom.:

690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.0632

Gnomad ASJ

AF:

0.0660

Gnomad EAS

AF:

0.0166

Gnomad SAS

AF:

0.0284

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.0684

GnomAD2 exomes

AF:

0.0814

AC:

19968

AN:

245250

AF XY:

0.0809

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.0408

Gnomad ASJ exome

AF:

0.0604

Gnomad EAS exome

AF:

0.0130

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0830

GnomAD4 exome

AF:

0.101

AC:

147128

AN:

1460098

Hom.:

8423

Cov.:

AF XY:

0.0986

AC XY:

71643

AN XY:

726290

show subpopulations

African (AFR)

AF:

0.0193

AC:

646

AN:

33474

American (AMR)

AF:

0.0424

AC:

1892

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.0597

AC:

1560

AN:

26122

East Asian (EAS)

AF:

0.0352

AC:

1398

AN:

39698

South Asian (SAS)

AF:

0.0293

AC:

2522

AN:

86136

European-Finnish (FIN)

AF:

0.195

AC:

10187

AN:

52270

Middle Eastern (MID)

AF:

0.0260

AC:

150

AN:

5766

European-Non Finnish (NFE)

AF:

0.111

AC:

123717

AN:

1111622

Other (OTH)

AF:

0.0838

AC:

5056

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8431

16862

25294

33725

42156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4350

8700

13050

17400

21750

<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:

0.0804

AC:

12229

AN:

152142

Hom.:

691

Cov.:

AF XY:

0.0839

AC XY:

6242

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0225

AC:

933

AN:

41528

American (AMR)

AF:

0.0630

AC:

964

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0660

AC:

229

AN:

3468

East Asian (EAS)

AF:

0.0164

AC:

AN:

5178

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4828

European-Finnish (FIN)

AF:

0.204

AC:

2151

AN:

10560

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7432

AN:

67970

Other (OTH)

AF:

0.0682

AC:

144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

548

1096

1645

2193

2741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0945

Hom.:

1992

Bravo

AF:

0.0669

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

MHC class I deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.1

(source)

DANN

Benign

0.49

PhyloP100

-2.1

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)

0.030

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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