6-32830705-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001290043.2(TAP2):c.1374G>A(p.Thr458Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,613,042 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. T458T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 36 hom. )

Consequence

TAP2
NM_001290043.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -4.27

Publications

3 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 6-32830705-C-T is Benign according to our data. Variant chr6-32830705-C-T is described in ClinVar as Benign. ClinVar VariationId is 466366.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.27 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1627/152300) while in subpopulation AFR AF = 0.0298 (1240/41550). AF 95% confidence interval is 0.0285. There are 28 homozygotes in GnomAd4. There are 807 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1374G>A	p.Thr458Thr	synonymous_variant	Exon 8 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3 link	c.1374G>A	p.Thr458Thr	synonymous_variant	Exon 8 of 12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1374G>A	p.Thr458Thr	synonymous_variant	Exon 8 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2 link	c.1374G>A	p.Thr458Thr	synonymous_variant	Exon 8 of 15	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1620

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.00476

AC:

1174

AN:

246544

AF XY:

0.00367

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.000301

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00192

Gnomad OTH exome

AF:

0.00889

GnomAD4 exome

AF:

0.00270

AC:

3945

AN:

1460742

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

1831

AN XY:

726694

show subpopulations

African (AFR)

AF:

0.0274

AC:

917

AN:

33478

American (AMR)

AF:

0.0133

AC:

593

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000313

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.000153

AC:

AN:

52316

Middle Eastern (MID)

AF:

0.00659

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00179

AC:

1991

AN:

1111998

Other (OTH)

AF:

0.00603

AC:

364

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

245

491

736

982

1227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0107

AC:

1627

AN:

152300

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

807

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0298

AC:

1240

AN:

41550

American (AMR)

AF:

0.0138

AC:

211

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00206

AC:

140

AN:

68026

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

158

237

316

395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00490

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

TAP2-related disorder

Benign:1

Apr 01, 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

-0.74

CADD

Benign

0.29

(source)

DANN

Benign

0.47

PhyloP100

-4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(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