Genetic Variant TAP2:c.1273-148G>A (chr6-32830954-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001290043.2(TAP2):c.1273-148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 823,902 control chromosomes in the GnomAD database, including 39,571 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 0.28 ( 6707 hom., cov: 32)

Exomes 𝑓: 0.30 ( 32864 hom. )

Consequence

TAP2
NM_001290043.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391

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 links:

ENSG00000250264 (HGNC:):

ENSG00000250264 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1273-148G>A		intron_variant	Intron 7 of 11	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1273-148G>A		intron_variant	Intron 7 of 11		NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1273-148G>A		intron_variant	Intron 7 of 11	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1273-148G>A		intron_variant	Intron 7 of 14	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43021

AN:

151974

Hom.:

6696

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.343

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.233

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.300

AC:

201798

AN:

671810

Hom.:

32864

AF XY:

0.299

AC XY:

106237

AN XY:

355344

show subpopulations

Gnomad4 AFR exome

AF:

0.187

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.240

Gnomad4 FIN exome

AF:

0.476

Gnomad4 NFE exome

AF:

0.319

Gnomad4 OTH exome

AF:

0.284

GnomAD4 genome

AF:

0.283

AC:

43054

AN:

152092

Hom.:

6707

Cov.:

AF XY:

0.289

AC XY:

21475

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.201

Gnomad4 EAS

AF:

0.282

Gnomad4 SAS

AF:

0.235

Gnomad4 FIN

AF:

0.499

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.307

Hom.:

6118

Bravo

AF:

0.256

Asia WGS

AF:

0.216

AC:

752

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.44

DANN

Benign

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over