6-32832444-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001290043.2(TAP2):c.1161G>A(p.Val387Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,612,722 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 46 hom., cov: 32)

Exomes 𝑓: 0.024 ( 524 hom. )

Consequence

TAP2
NM_001290043.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.65

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: 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 6-32832444-C-T is Benign according to our data. Variant chr6-32832444-C-T is described in ClinVar as [Benign]. Clinvar id is 466365.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.65 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0204 (3105/152320) while in subpopulation AMR AF = 0.0283 (433/15302). AF 95% confidence interval is 0.0261. There are 46 homozygotes in GnomAd4. There are 1378 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 12		NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 15	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3104

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0234

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0145

AC:

3561

AN:

245660

AF XY:

0.0139

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.0182

Gnomad ASJ exome

AF:

0.00673

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00315

Gnomad NFE exome

AF:

0.0215

Gnomad OTH exome

AF:

0.0192

GnomAD4 exome

AF:

0.0242

AC:

35398

AN:

1460402

Hom.:

524

Cov.:

AF XY:

0.0230

AC XY:

16727

AN XY:

726462

show subpopulations

African (AFR)

AF:

0.0209

AC:

701

AN:

33472

American (AMR)

AF:

0.0197

AC:

880

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00750

AC:

196

AN:

26130

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00354

AC:

185

AN:

52312

Middle Eastern (MID)

AF:

0.00452

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0288

AC:

32071

AN:

1111816

Other (OTH)

AF:

0.0220

AC:

1329

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2075

4149

6224

8298

10373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0204

AC:

3105

AN:

152320

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1378

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0232

AC:

962

AN:

41552

American (AMR)

AF:

0.0283

AC:

433

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00179

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0234

AC:

1591

AN:

68028

Other (OTH)

AF:

0.0298

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

145

290

435

580

725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0192

Hom.:

Bravo

AF:

0.0233

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0234

EpiControl

AF:

0.0234

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

- -

TAP2-related disorder

Benign:1

May 09, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

5.9

(source)

DANN

Benign

0.72

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=81/19

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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6-32832444-C-T

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