Genetic Variant ENSG00000250264:c.1933-5330A>G (chr6-32822282-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_018833.3(TAP2):c.*7A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,550,926 control chromosomes in the GnomAD database, including 1,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.037 ( 138 hom., cov: 32)

Exomes 𝑓: 0.034 ( 984 hom. )

Consequence

TAP2
NM_018833.3 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.519

Variant links:

Genes affected

ENSG00000250264 (HGNC:):

ENSG00000250264 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-32822282-T-C is Benign according to our data. Variant chr6-32822282-T-C is described in ClinVar as [Benign]. Clinvar id is 3060503.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.053 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_018833.3 link	c.*7A>G		3_prime_UTR_variant	Exon 12 of 12		NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250264	ENST00000452392.2 link	c.1933-5330A>G		intron_variant	Intron 11 of 14	2		ENSP00000391806.2		E7ENX8
TAP2	ENST00000652259 link	c.*7A>G		3_prime_UTR_variant	Exon 12 of 12			ENSP00000498827.1		Q03519-2

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5690

AN:

152048

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0462

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0561

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.00288

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0375

Gnomad OTH

AF:

0.0598

GnomAD3 exomes

AF:

0.0281

AC:

5877

AN:

209392

Hom.:

142

AF XY:

0.0271

AC XY:

3057

AN XY:

112994

show subpopulations

Gnomad AFR exome

AF:

0.0472

Gnomad AMR exome

AF:

0.0407

Gnomad ASJ exome

AF:

0.0441

Gnomad EAS exome

AF:

0.00127

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.00236

Gnomad NFE exome

AF:

0.0356

Gnomad OTH exome

AF:

0.0449

GnomAD4 exome

AF:

0.0342

AC:

47786

AN:

1398762

Hom.:

984

Cov.:

AF XY:

0.0331

AC XY:

23009

AN XY:

695250

show subpopulations

Gnomad4 AFR exome

AF:

0.0446

Gnomad4 AMR exome

AF:

0.0452

Gnomad4 ASJ exome

AF:

0.0441

Gnomad4 EAS exome

AF:

0.000713

Gnomad4 SAS exome

AF:

0.00467

Gnomad4 FIN exome

AF:

0.00370

Gnomad4 NFE exome

AF:

0.0383

Gnomad4 OTH exome

AF:

0.0321

GnomAD4 genome

AF:

0.0374

AC:

5691

AN:

152164

Hom.:

138

Cov.:

AF XY:

0.0354

AC XY:

2632

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0461

Gnomad4 AMR

AF:

0.0561

Gnomad4 ASJ

AF:

0.0446

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.0375

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0395

Hom.:

239

Bravo

AF:

0.0446

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TAP2-related disorder

Benign:1

Apr 29, 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

-0.90

CADD

Benign

8.1

DANN

Benign

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over