chr6-32830954-C-T

Variant names:

• chr6-32830954-C-T
• rs1015166
• NM_001290043.2:c.1273-148G>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 43 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 (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	c.1273-148G>A		intron_variant	Intron 7 of 11	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1273-148G>A		intron_variant	Intron 7 of 11		NP_061313.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43021 AN: 151974 Hom.: 6696 Cov.: 32

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

African (AFR) AF: 0.187 AC: 3359 AN: 17968

American (AMR) AF: 0.186 AC: 6431 AN: 34544

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 3923 AN: 20604

East Asian (EAS) AF: 0.274 AC: 8913 AN: 32576

South Asian (SAS) AF: 0.240 AC: 15474 AN: 64448

European-Finnish (FIN) AF: 0.476 AC: 16161 AN: 33952

Middle Eastern (MID) AF: 0.196 AC: 544 AN: 2770

European-Non Finnish (NFE) AF: 0.319 AC: 137229 AN: 430568

Other (OTH) AF: 0.284 AC: 9764 AN: 34380

GnomAD4 genome AF: 0.283 AC: 43054 AN: 152092 Hom.: 6707 Cov.: 32 AF XY: 0.289 AC XY: 21475 AN XY: 74322

African (AFR) AF: 0.190 AC: 7895 AN: 41508

American (AMR) AF: 0.223 AC: 3408 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1460 AN: 5172

South Asian (SAS) AF: 0.235 AC: 1129 AN: 4810

European-Finnish (FIN) AF: 0.499 AC: 5260 AN: 10550

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.328 AC: 22299 AN: 67974

Other (OTH) AF: 0.256 AC: 541 AN: 2110

Alfa AF: 0.303 Hom.: 20037

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
PhyloP100		-0.39
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: rs1015166; hg19: chr6-32798731;