dbSNP rs183585: TAP2:c.1272+437C>T (chr6-32831896-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001290043.2(TAP2):c.1272+437C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,216 control chromosomes in the GnomAD database, including 4,697 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4697 hom., cov: 33)

Consequence

TAP2
NM_001290043.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.193

Publications

7 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 -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1272+437C>T		intron_variant	Intron 7 of 11	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3 link	c.1272+437C>T		intron_variant	Intron 7 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1272+437C>T		intron_variant	Intron 7 of 11	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2 link	c.1272+437C>T		intron_variant	Intron 7 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37218

AN:

152098

Hom.:

4684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.282

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.251

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.245

AC:

37268

AN:

152216

Hom.:

4697

Cov.:

AF XY:

0.243

AC XY:

18051

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.231

AC:

9608

AN:

41514

American (AMR)

AF:

0.307

AC:

4690

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

980

AN:

3470

East Asian (EAS)

AF:

0.253

AC:

1315

AN:

5190

South Asian (SAS)

AF:

0.277

AC:

1337

AN:

4826

European-Finnish (FIN)

AF:

0.185

AC:

1962

AN:

10598

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16592

AN:

68002

Other (OTH)

AF:

0.251

AC:

531

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1438

2876

4314

5752

7190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.247

Hom.:

4178

Bravo

AF:

0.255

Asia WGS

AF:

0.292

AC:

1013

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.7

(source)

DANN

Benign

0.82

PhyloP100

-0.19

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over