6-32826899-T-C

Variant names:

• chr6-32826899-T-C
• rs2857101
• NM_001290043.2:c.*2007A>G

Variant summary

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

The NM_001290043.2(TAP2):​c.*2007A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 985,176 control chromosomes in the GnomAD database, including 31,362 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 0.25 (5205 hom., cov: 32)
  • Exomes 𝑓: 0.25 (26157 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 41 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 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.*2007A>G		3_prime_UTR	Exon 12 of 12	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1932+2501A>G		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.*2007A>G		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+2501A>G		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698440.1		c.*2007A>G		3_prime_UTR	Exon 13 of 13	ENSP00000513722.1	Q03519-1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37807 AN: 152036 Hom.: 5199 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.247 AC: 205931 AN: 833022 Hom.: 26157 Cov.: 33 AF XY: 0.247 AC XY: 95062 AN XY: 384678

African (AFR) AF: 0.141 AC: 2218 AN: 15784

American (AMR) AF: 0.313 AC: 307 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1764 AN: 5152

East Asian (EAS) AF: 0.349 AC: 1266 AN: 3630

South Asian (SAS) AF: 0.410 AC: 6739 AN: 16456

European-Finnish (FIN) AF: 0.338 AC: 94 AN: 278

Middle Eastern (MID) AF: 0.274 AC: 444 AN: 1620

European-Non Finnish (NFE) AF: 0.244 AC: 186114 AN: 761826

Other (OTH) AF: 0.256 AC: 6985 AN: 27294

GnomAD4 genome AF: 0.249 AC: 37829 AN: 152154 Hom.: 5205 Cov.: 32 AF XY: 0.257 AC XY: 19140 AN XY: 74384

African (AFR) AF: 0.140 AC: 5806 AN: 41530

American (AMR) AF: 0.315 AC: 4822 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1178 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1850 AN: 5176

South Asian (SAS) AF: 0.387 AC: 1866 AN: 4824

European-Finnish (FIN) AF: 0.344 AC: 3633 AN: 10564

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17671 AN: 67980

Other (OTH) AF: 0.269 AC: 567 AN: 2108

Alfa AF: 0.254 Hom.: 18236

Bravo AF: 0.241

Asia WGS AF: 0.342 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		0.17
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: rs2857101; hg19: chr6-32794676;