ENST00000452392.2:c.1933-5371delT

Variant names:

• chr6-32822322-GA-G
• rs61021012
• ENST00000452392.2:c.1933-5371delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000452392.2(ENSG00000250264):​c.1933-5371delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,325,670 control chromosomes in the GnomAD database, including 384 homozygotes. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0083 (27 hom., cov: 31)
  • Exomes 𝑓: 0.013 (357 hom.)
• Consequence: ENSG00000250264 ENST00000452392.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452392.2. 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_018833.3		c.1933-5delT		splice_region intron	N/A	NP_061313.2	Q9UP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1933-5371delT		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000652259.1		c.1933-5delT		splice_region intron	N/A	ENSP00000498827.1	Q03519-2
	ENSG00000307274	ENST00000824890.1		n.79+1443delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00832 AC: 1197 AN: 143840 Hom.: 27 Cov.: 31

Gnomad AFR AF: 0.00156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00802

Gnomad ASJ AF: 0.0342

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.000576

Gnomad MID AF: 0.0229

Gnomad NFE AF: 0.00519

Gnomad OTH AF: 0.0111

GnomAD2 exomes AF: 0.0346 AC: 2722 AN: 78718 AF XY: 0.0407

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0714

Gnomad EAS exome AF: 0.0206

Gnomad FIN exome AF: 0.00106

Gnomad NFE exome AF: 0.0145

Gnomad OTH exome AF: 0.0378

GnomAD4 exome AF: 0.0130 AC: 15386 AN: 1181760 Hom.: 357 Cov.: 27 AF XY: 0.0156 AC XY: 9125 AN XY: 584830

African (AFR) AF: 0.00241 AC: 59 AN: 24472

American (AMR) AF: 0.0109 AC: 302 AN: 27726

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 856 AN: 21088

East Asian (EAS) AF: 0.0738 AC: 2410 AN: 32676

South Asian (SAS) AF: 0.0912 AC: 5945 AN: 65198

European-Finnish (FIN) AF: 0.000525 AC: 22 AN: 41934

Middle Eastern (MID) AF: 0.0363 AC: 171 AN: 4710

European-Non Finnish (NFE) AF: 0.00530 AC: 4850 AN: 915532

Other (OTH) AF: 0.0159 AC: 771 AN: 48424

GnomAD4 genome AF: 0.00832 AC: 1198 AN: 143910 Hom.: 27 Cov.: 31 AF XY: 0.00950 AC XY: 663 AN XY: 69784

African (AFR) AF: 0.00155 AC: 61 AN: 39272

American (AMR) AF: 0.00801 AC: 116 AN: 14476

Ashkenazi Jewish (ASJ) AF: 0.0342 AC: 115 AN: 3358

East Asian (EAS) AF: 0.0282 AC: 141 AN: 5004

South Asian (SAS) AF: 0.0854 AC: 392 AN: 4588

European-Finnish (FIN) AF: 0.000576 AC: 5 AN: 8680

Middle Eastern (MID) AF: 0.0282 AC: 8 AN: 284

European-Non Finnish (NFE) AF: 0.00519 AC: 339 AN: 65370

Other (OTH) AF: 0.0105 AC: 21 AN: 1996

Alfa AF: 0.00957 Hom.: 5

Bravo AF: 0.00621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
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: rs61021012; hg19: chr6-32790099;