6-32822322-GAA-GAAAA

Variant names:

• chr6-32822322-G-GAA
• rs61021012
• ENST00000452392.2:c.1933-5371_1933-5370insTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000452392.2(ENSG00000250264):​c.1933-5371_1933-5370insTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,323,196 control chromosomes in the GnomAD database, including 9 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0010 (4 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00176 (254/143916) while in subpopulation EAS AF = 0.0482 (241/5002). AF 95% confidence interval is 0.0432. There are 5 homozygotes in GnomAd4. There are 142 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_018833.3		c.1933-6_1933-5dupTT		splice_region intron	N/A	NP_061313.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1933-5371_1933-5370insTT		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000652259.1		c.1933-5_1933-4insTT		splice_region intron	N/A	ENSP00000498827.1
	ENSG00000307274	ENST00000824890.1		n.79+1442_79+1443insAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 254 AN: 143846 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0000510

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000207

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0481

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000612

Gnomad OTH AF: 0.00202

GnomAD2 exomes AF: 0.00640 AC: 504 AN: 78718 AF XY: 0.00597

Gnomad AFR exome AF: 0.000663

Gnomad AMR exome AF: 0.00108

Gnomad ASJ exome AF: 0.00121

Gnomad EAS exome AF: 0.0758

Gnomad FIN exome AF: 0.000193

Gnomad NFE exome AF: 0.000824

Gnomad OTH exome AF: 0.00466

GnomAD4 exome AF: 0.00102 AC: 1200 AN: 1179280 Hom.: 4 Cov.: 27 AF XY: 0.000994 AC XY: 580 AN XY: 583682

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00127 AC: 31 AN: 24416

American (AMR) AF: 0.000832 AC: 23 AN: 27656

Ashkenazi Jewish (ASJ) AF: 0.000380 AC: 8 AN: 21046

East Asian (EAS) AF: 0.0207 AC: 673 AN: 32540

South Asian (SAS) AF: 0.000261 AC: 17 AN: 65122

European-Finnish (FIN) AF: 0.000478 AC: 20 AN: 41840

Middle Eastern (MID) AF: 0.000212 AC: 1 AN: 4714

European-Non Finnish (NFE) AF: 0.000387 AC: 354 AN: 913662

Other (OTH) AF: 0.00151 AC: 73 AN: 48284

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00176 AC: 254 AN: 143916 Hom.: 5 Cov.: 31 AF XY: 0.00203 AC XY: 142 AN XY: 69792

African (AFR) AF: 0.0000509 AC: 2 AN: 39272

American (AMR) AF: 0.000207 AC: 3 AN: 14476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3358

East Asian (EAS) AF: 0.0482 AC: 241 AN: 5002

South Asian (SAS) AF: 0.00 AC: 0 AN: 4590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000612 AC: 4 AN: 65376

Other (OTH) AF: 0.00200 AC: 4 AN: 1996

Alfa AF: 0.000797 Hom.: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61021012; hg19: chr6-32790099; COSMIC: COSV105930570; COSMIC: COSV105930570;