chr6-32832635-C-T

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.1135G>A(p.Val379Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,612,908 control chromosomes in the GnomAD database, including 16,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V379L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.14 ( 1653 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14813 hom. )

Consequence

TAP2
NM_001290043.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -2.53

Publications

67 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=0.002161771).

BP6

Variant 6-32832635-C-T is Benign according to our data. Variant chr6-32832635-C-T is described in ClinVar as Benign. ClinVar VariationId is 13724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1135G>A	p.Val379Ile	missense_variant	Exon 6 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3 link	c.1135G>A	p.Val379Ile	missense_variant	Exon 6 of 12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1135G>A	p.Val379Ile	missense_variant	Exon 6 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2 link	c.1135G>A	p.Val379Ile	missense_variant	Exon 6 of 15	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21865

AN:

152028

Hom.:

1650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0895

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.144

AC:

35501

AN:

246610

AF XY:

0.140

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.201

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.140

AC:

204942

AN:

1460762

Hom.:

14813

Cov.:

AF XY:

0.139

AC XY:

100866

AN XY:

726696

show subpopulations

African (AFR)

AF:

0.148

AC:

4963

AN:

33478

American (AMR)

AF:

0.163

AC:

7284

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

3150

AN:

26136

East Asian (EAS)

AF:

0.168

AC:

6681

AN:

39698

South Asian (SAS)

AF:

0.0904

AC:

7794

AN:

86258

European-Finnish (FIN)

AF:

0.139

AC:

7297

AN:

52316

Middle Eastern (MID)

AF:

0.153

AC:

884

AN:

5768

European-Non Finnish (NFE)

AF:

0.142

AC:

158158

AN:

1111998

Other (OTH)

AF:

0.145

AC:

8731

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11972

23943

35915

47886

59858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5680

11360

17040

22720

28400

<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:

0.144

AC:

21888

AN:

152146

Hom.:

1653

Cov.:

AF XY:

0.144

AC XY:

10704

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.153

AC:

6335

AN:

41500

American (AMR)

AF:

0.139

AC:

2120

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

404

AN:

3472

East Asian (EAS)

AF:

0.186

AC:

966

AN:

5182

South Asian (SAS)

AF:

0.0889

AC:

428

AN:

4814

European-Finnish (FIN)

AF:

0.146

AC:

1541

AN:

10586

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9622

AN:

67996

Other (OTH)

AF:

0.136

AC:

286

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

962

1924

2887

3849

4811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<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:

0.141

Hom.:

7115

Bravo

AF:

0.146

TwinsUK

AF:

0.146

AC:

543

ALSPAC

AF:

0.145

AC:

557

ESP6500AA

AF:

0.149

AC:

450

ESP6500EA

AF:

0.137

AC:

742

ExAC

AF:

0.142

AC:

16766

Asia WGS

AF:

0.164

AC:

572

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:2

Jul 15, 2021

Genome-Nilou Lab

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 -

TAP2 POLYMORPHISM

Benign:1

May 01, 1992

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

not provided

Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.0020

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.14

.;.;.;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.44

T;.;.;.

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.34

.;N;.;N

PhyloP100

-2.5

PrimateAI

Benign

0.35

PROVEAN

Benign

0.23

N;N;.;N

REVEL

Benign

0.20

Sift

Benign

0.49

T;T;.;T

Sift4G

Benign

0.85

.;T;T;T

Polyphen

0.029

.;.;.;B

Vest4

0.070, 0.071

MPC

0.37

ClinPred

0.0078

GERP RS

-9.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.11

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

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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