NM_001290043.2:c.945+728C>A

Variant names:

• chr6-32834426-G-T
• rs241432
• NM_001290043.2:c.945+728C>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.945+728C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 152,068 control chromosomes in the GnomAD database, including 25,556 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 (25556 hom., cov: 32)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 24 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ENSG00000250264 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290043.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.945+728C>A		intron	N/A	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.945+728C>A		intron	N/A	NP_061313.2	Q9UP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.945+728C>A		intron	N/A	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.945+728C>A		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698449.1		c.945+728C>A		intron	N/A	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87525 AN: 151950 Hom.: 25519 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.576 AC: 87613 AN: 152068 Hom.: 25556 Cov.: 32 AF XY: 0.578 AC XY: 42990 AN XY: 74326

African (AFR) AF: 0.504 AC: 20892 AN: 41458

American (AMR) AF: 0.565 AC: 8635 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1828 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2889 AN: 5176

South Asian (SAS) AF: 0.588 AC: 2837 AN: 4822

European-Finnish (FIN) AF: 0.694 AC: 7334 AN: 10570

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41283 AN: 67976

Other (OTH) AF: 0.547 AC: 1154 AN: 2110

Alfa AF: 0.579 Hom.: 39935

Bravo AF: 0.560

Asia WGS AF: 0.553 AC: 1920 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.41
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs241432; hg19: chr6-32802203;