6-32822322-GA-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018833.3(TAP2):c.1933-5_1933-4insT 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 0.0834 in 1,113,954 control chromosomes in the GnomAD database, including 340 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (139 hom., cov: 31)
  • Exomes 𝑓: 0.089 (201 hom.)
• Consequence: TAP2 NM_018833.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 6-32822322-G-GA is Benign according to our data. Variant chr6-32822322-G-GA is described in ClinVar as [Benign]. Clinvar id is 403508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6187 AN: 143676 Hom.: 139 Cov.: 31

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.0115

Gnomad FIN AF: 0.0564

Gnomad MID AF: 0.0163

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0294

GnomAD4 exome AF: 0.0894 AC: 86690 AN: 970208 Hom.: 201 Cov.: 27 AF XY: 0.0892 AC XY: 42464 AN XY: 475832

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.0940

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.0633

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.0881

Gnomad4 OTH exome AF: 0.0922

GnomAD4 genome AF: 0.0431 AC: 6191 AN: 143746 Hom.: 139 Cov.: 31 AF XY: 0.0440 AC XY: 3067 AN XY: 69694

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.0361

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0374

Gnomad4 SAS AF: 0.0115

Gnomad4 FIN AF: 0.0564

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.0327

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;