6-32822322-GA-GAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_018833.3(TAP2):c.1933-5_1933-4insTT variant causes a splice region, splice polypyrimidine tract, 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: TAP2 NM_018833.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_018833.3	c.1933-5_1933-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000652259.1	c.1933-5_1933-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

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

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

Gnomad4 AFR exome AF: 0.00127

Gnomad4 AMR exome AF: 0.000832

Gnomad4 ASJ exome AF: 0.000380

Gnomad4 EAS exome AF: 0.0207

Gnomad4 SAS exome AF: 0.000261

Gnomad4 FIN exome AF: 0.000478

Gnomad4 NFE exome AF: 0.000387

Gnomad4 OTH exome AF: 0.00151

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

Gnomad4 AFR AF: 0.0000509

Gnomad4 AMR AF: 0.000207

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0482

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000612

Gnomad4 OTH AF: 0.00200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61021012; hg19: chr6-32790099;