rs28724898

Positions:

• chr6-32835631-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001290043.2(TAP2):​c.739+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,612,946 control chromosomes in the GnomAD database, including 1,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (251 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1330 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.190

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-32835631-T-A is Benign according to our data. Variant chr6-32835631-T-A is described in ClinVar as [Benign]. Clinvar id is 403517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.739+12A>T		intron_variant		ENST00000374897.4
TAP2	NM_018833.3	c.739+12A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.739+12A>T		intron_variant		1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7628 AN: 152092 Hom.: 250 Cov.: 31

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0762

Gnomad FIN AF: 0.00895

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0375 AC: 9254 AN: 246556 Hom.: 234 AF XY: 0.0394 AC XY: 5299 AN XY: 134396

Gnomad AFR exome AF: 0.0888

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0394

Gnomad EAS exome AF: 0.0189

Gnomad SAS exome AF: 0.0667

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0339

GnomAD4 exome AF: 0.0384 AC: 56027 AN: 1460736 Hom.: 1330 Cov.: 33 AF XY: 0.0390 AC XY: 28312 AN XY: 726686

Gnomad4 AFR exome AF: 0.0907

Gnomad4 AMR exome AF: 0.0254

Gnomad4 ASJ exome AF: 0.0393

Gnomad4 EAS exome AF: 0.00904

Gnomad4 SAS exome AF: 0.0646

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.0373

Gnomad4 OTH exome AF: 0.0425

GnomAD4 genome AF: 0.0502 AC: 7639 AN: 152210 Hom.: 251 Cov.: 31 AF XY: 0.0487 AC XY: 3626 AN XY: 74426

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.0208

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.00895

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0423 Hom.: 26

Bravo AF: 0.0515

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

MHC class I deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.7
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs28724898; hg19: chr6-32803408;