chr6-32822390-C-G

Variant names:

• chr6-32822390-C-G
• rs2857104
• ENST00000452392.2:c.1933-5438G>C

Variant summary

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

The ENST00000452392.2(ENSG00000250264):​c.1933-5438G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,004,268 control chromosomes in the GnomAD database, including 40,230 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 0.26 (5539 hom., cov: 32)
  • Exomes 𝑓: 0.28 (34691 hom.)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• Publications: 11 publications found

Genes affected

ENSG00000250264 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_018833.3	c.1933-72G>C		intron_variant	Intron 11 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000250264	ENST00000452392.2	c.1933-5438G>C		intron_variant	Intron 11 of 14	2		ENSP00000391806.2
TAP2	ENST00000652259.1	c.1933-72G>C		intron_variant	Intron 11 of 11			ENSP00000498827.1
ENSG00000307274	ENST00000824890.1	n.79+1510C>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39157 AN: 151440 Hom.: 5534 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.276 AC: 235276 AN: 852728 Hom.: 34691 AF XY: 0.280 AC XY: 122870 AN XY: 439170

African (AFR) AF: 0.165 AC: 2966 AN: 17940

American (AMR) AF: 0.381 AC: 8150 AN: 21414

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 6813 AN: 19792

East Asian (EAS) AF: 0.354 AC: 11551 AN: 32652

South Asian (SAS) AF: 0.382 AC: 23384 AN: 61158

European-Finnish (FIN) AF: 0.340 AC: 15582 AN: 45768

Middle Eastern (MID) AF: 0.288 AC: 890 AN: 3088

European-Non Finnish (NFE) AF: 0.254 AC: 155347 AN: 611970

Other (OTH) AF: 0.272 AC: 10593 AN: 38946

GnomAD4 genome AF: 0.259 AC: 39176 AN: 151540 Hom.: 5539 Cov.: 32 AF XY: 0.268 AC XY: 19803 AN XY: 74018

African (AFR) AF: 0.159 AC: 6581 AN: 41350

American (AMR) AF: 0.350 AC: 5340 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1177 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1859 AN: 5176

South Asian (SAS) AF: 0.388 AC: 1864 AN: 4804

European-Finnish (FIN) AF: 0.352 AC: 3625 AN: 10304

Middle Eastern (MID) AF: 0.290 AC: 84 AN: 290

European-Non Finnish (NFE) AF: 0.261 AC: 17706 AN: 67896

Other (OTH) AF: 0.279 AC: 586 AN: 2102

Alfa AF: 0.245 Hom.: 656

Bravo AF: 0.253

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.54
PhyloP100		-0.78
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: rs2857104; hg19: chr6-32790167;