6-32822282-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.037 (138 hom., cov: 32)
  • Exomes 𝑓: 0.034 (984 hom.)
• Consequence: TAP2 NM_018833.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.519

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]

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
TAP2	NM_018833.3	c.*7A>G		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000652259.1	c.*7A>G		3_prime_UTR_variant	12/12

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5690 AN: 152048 Hom.: 136 Cov.: 32

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

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.: 27 AF XY: 0.0331 AC XY: 23009 AN XY: 695250

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.: 32 AF XY: 0.0354 AC XY: 2632 AN XY: 74386

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: 35 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TAP2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2019

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

Other links and lift over

dbSNP: rs2857105; hg19: chr6-32790059;