chr6-32831018-C-A

Variant names:

• chr6-32831018-C-A
• rs241433
• NM_001290043.2:c.1273-212G>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.1273-212G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,944 control chromosomes in the GnomAD database, including 25,641 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 0.58 (25641 hom., cov: 31)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 31 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.1273-212G>T		intron_variant	Intron 7 of 11	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1273-212G>T		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.1273-212G>T		intron_variant	Intron 7 of 11	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1273-212G>T		intron_variant	Intron 7 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87644 AN: 151828 Hom.: 25604 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.544

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.577 AC: 87732 AN: 151944 Hom.: 25641 Cov.: 31 AF XY: 0.579 AC XY: 43028 AN XY: 74270

African (AFR) AF: 0.504 AC: 20887 AN: 41404

American (AMR) AF: 0.566 AC: 8643 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2877 AN: 5158

South Asian (SAS) AF: 0.588 AC: 2835 AN: 4822

European-Finnish (FIN) AF: 0.693 AC: 7317 AN: 10556

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.610 AC: 41424 AN: 67946

Other (OTH) AF: 0.548 AC: 1154 AN: 2106

Alfa AF: 0.598 Hom.: 111067

Bravo AF: 0.561

Asia WGS AF: 0.552 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.029
DANN	Benign	0.54
PhyloP100		-1.7
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: rs241433; hg19: chr6-32798795;