NM_001290043.2:c.1920G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_001290043.2(TAP2):c.1920G>A(p.Gln640Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000671 in 1,604,242 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 1 hom. )

Consequence

TAP2
NM_001290043.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0430

Publications

2 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 6-32829412-C-T is Benign according to our data. Variant chr6-32829412-C-T is described in ClinVar as Benign. ClinVar VariationId is 534715.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.043 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000505 (77/152344) while in subpopulation AMR AF = 0.00222 (34/15312). AF 95% confidence interval is 0.00163. There are 0 homozygotes in GnomAd4. There are 39 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.1920G>A	p.Gln640Gln	synonymous	Exon 11 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.1920G>A	p.Gln640Gln	synonymous	Exon 11 of 12	NP_061313.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TAP2	ENST00000374897.4	TSL:1 MANE Select	c.1920G>A	p.Gln640Gln	synonymous	Exon 11 of 12	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	TSL:2	c.1920G>A	p.Gln640Gln	synonymous	Exon 11 of 15	ENSP00000391806.2
TAP2	ENST00000698449.1		c.1953G>A	p.Gln651Gln	synonymous	Exon 12 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000623

AC:

146

AN:

234268

AF XY:

0.000666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000496

Gnomad NFE exome

AF:

0.000637

Gnomad OTH exome

AF:

0.000856

GnomAD4 exome

AF:

0.000689

AC:

1000

AN:

1451898

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

499

AN XY:

721146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33372

American (AMR)

AF:

0.00171

AC:

AN:

43180

Ashkenazi Jewish (ASJ)

AF:

0.00190

AC:

AN:

25794

East Asian (EAS)

AF:

0.00

AC:

AN:

39498

South Asian (SAS)

AF:

0.00

AC:

AN:

84566

European-Finnish (FIN)

AF:

0.000171

AC:

AN:

52688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.000722

AC:

799

AN:

1107028

Other (OTH)

AF:

0.00115

AC:

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

130

196

261

326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.000505

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41580

American (AMR)

AF:

0.00222

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000637

Hom.:

Bravo

AF:

0.000608

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:1

Jan 10, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

5.7

(source)

DANN

Benign

0.60

PhyloP100

-0.043

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over