rs61021012

chr6-32822322-GA-Gchr6-32822322-GA-GAAchr6-32822322-GA-GAAAchr6-32822322-GA-GAAAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_018833.3(TAP2):c.1933-5del 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 0.0125 in 1,325,670 control chromosomes in the GnomAD database, including 384 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0083 (27 hom., cov: 31)
  • Exomes 𝑓: 0.013 (357 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 -9 ACMG points.

• BP6: Variant 6-32822322-GA-G is Benign according to our data. Variant chr6-32822322-GA-G is described in Lovd as [Benign]. Variant chr6-32822322-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0785 is higher than 0.05.

Transcripts

RefSeq

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

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

GnomAD3 exomes AF: 0.0346 AC: 2722 AN: 78718 Hom.: 61 AF XY: 0.0407 AC XY: 1724 AN XY: 42408

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 SAS exome AF: 0.155

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

Gnomad4 AFR exome AF: 0.00241

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.0406

Gnomad4 EAS exome AF: 0.0738

Gnomad4 SAS exome AF: 0.0912

Gnomad4 FIN exome AF: 0.000525

Gnomad4 NFE exome AF: 0.00530

Gnomad4 OTH exome AF: 0.0159

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

Gnomad4 AFR AF: 0.00155

Gnomad4 AMR AF: 0.00801

Gnomad4 ASJ AF: 0.0342

Gnomad4 EAS AF: 0.0282

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.000576

Gnomad4 NFE AF: 0.00519

Gnomad4 OTH AF: 0.0105

Alfa AF: 0.00957 Hom.: 5

Bravo AF: 0.00621

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs61021012; hg19: chr6-32790099;