rs241441

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.1812A>G(p.Gly604Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,613,800 control chromosomes in the GnomAD database, including 61,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5582 hom., cov: 32)

Exomes 𝑓: 0.27 ( 55787 hom. )

Consequence

TAP2
NM_001290043.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.69

Publications

36 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-32829520-T-C is Benign according to our data. Variant chr6-32829520-T-C is described in ClinVar as Benign. ClinVar VariationId is 403513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1812A>G	p.Gly604Gly	synonymous_variant	Exon 11 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1812A>G	p.Gly604Gly	synonymous_variant	Exon 11 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.1812A>G	p.Gly604Gly	synonymous_variant	Exon 11 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1812A>G	p.Gly604Gly	synonymous_variant	Exon 11 of 15	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39965

AN:

152036

Hom.:

5573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.387

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.303

AC:

76069

AN:

251004

AF XY:

0.306

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.349

Gnomad EAS exome

AF:

0.360

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.270

AC:

395196

AN:

1461646

Hom.:

55787

Cov.:

AF XY:

0.274

AC XY:

199227

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.183

AC:

6113

AN:

33478

American (AMR)

AF:

0.344

AC:

15359

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

9141

AN:

26126

East Asian (EAS)

AF:

0.351

AC:

13948

AN:

39700

South Asian (SAS)

AF:

0.395

AC:

34020

AN:

86228

European-Finnish (FIN)

AF:

0.339

AC:

18108

AN:

53392

Middle Eastern (MID)

AF:

0.294

AC:

1697

AN:

5764

European-Non Finnish (NFE)

AF:

0.252

AC:

279979

AN:

1111882

Other (OTH)

AF:

0.279

AC:

16831

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17761

35522

53283

71044

88805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9528

19056

28584

38112

47640

<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:

0.263

AC:

39995

AN:

152154

Hom.:

5582

Cov.:

AF XY:

0.271

AC XY:

20149

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.183

AC:

7609

AN:

41518

American (AMR)

AF:

0.321

AC:

4904

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1195

AN:

3470

East Asian (EAS)

AF:

0.360

AC:

1858

AN:

5162

South Asian (SAS)

AF:

0.400

AC:

1930

AN:

4824

European-Finnish (FIN)

AF:

0.345

AC:

3650

AN:

10588

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17806

AN:

67976

Other (OTH)

AF:

0.287

AC:

606

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1522

3043

4565

6086

7608

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.265

Hom.:

13533

Bravo

AF:

0.256

Asia WGS

AF:

0.362

AC:

1258

AN:

3478

EpiCase

AF:

0.266

EpiControl

AF:

0.269

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

(source)

DANN

Benign

0.65

PhyloP100

-3.7

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

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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