rs10484565

Variant names:

• chr6-32827255-G-A
• rs10484565
• NM_001290043.2:c.*1651C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290043.2(TAP2):​c.*1651C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 985,320 control chromosomes in the GnomAD database, including 2,735 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 0.062 (322 hom., cov: 32)
  • Exomes 𝑓: 0.073 (2413 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 46 publications found

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

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.*1651C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1932+2145C>T		intron_variant	Intron 11 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.*1651C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1932+2145C>T		intron_variant	Intron 11 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9385 AN: 152156 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0349

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.0880

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0417

GnomAD4 exome AF: 0.0732 AC: 61013 AN: 833046 Hom.: 2413 Cov.: 31 AF XY: 0.0731 AC XY: 28139 AN XY: 384688

African (AFR) AF: 0.0240 AC: 378 AN: 15770

American (AMR) AF: 0.0264 AC: 26 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 217 AN: 5152

East Asian (EAS) AF: 0.0719 AC: 261 AN: 3630

South Asian (SAS) AF: 0.0411 AC: 676 AN: 16460

European-Finnish (FIN) AF: 0.0993 AC: 28 AN: 282

Middle Eastern (MID) AF: 0.0660 AC: 107 AN: 1620

European-Non Finnish (NFE) AF: 0.0759 AC: 57812 AN: 761852

Other (OTH) AF: 0.0552 AC: 1508 AN: 27296

GnomAD4 genome AF: 0.0617 AC: 9398 AN: 152274 Hom.: 322 Cov.: 32 AF XY: 0.0623 AC XY: 4642 AN XY: 74456

African (AFR) AF: 0.0302 AC: 1257 AN: 41558

American (AMR) AF: 0.0348 AC: 533 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.0880 AC: 457 AN: 5192

South Asian (SAS) AF: 0.0450 AC: 217 AN: 4822

European-Finnish (FIN) AF: 0.108 AC: 1142 AN: 10590

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0809 AC: 5503 AN: 68016

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0774 Hom.: 2134

Bravo AF: 0.0551

Asia WGS AF: 0.0600 AC: 210 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	0.79
DANN	Benign	0.44
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10484565; hg19: chr6-32795032;