rs2857103

Variant names:

• chr6-32823522-C-A
• rs2857103
• ENST00000452392.2:c.1932+5878G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32823522-C-A
• chr6-32823522-C-G
• chr6-32823522-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018833.3(TAP2):​c.1933-1204G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 145,474 control chromosomes in the GnomAD database, including 9,650 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.37 (9650 hom., cov: 25)
• Consequence: TAP2 NM_018833.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 38 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018833.3. 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.1933-1204G>T		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.1932+5878G>T		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000652259.1		c.1933-1204G>T		intron	N/A	ENSP00000498827.1	Q03519-2
	ENSG00000307274	ENST00000824890.1		n.79+2642C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.367 AC: 53283 AN: 145364 Hom.: 9642 Cov.: 25

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.371

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.367 AC: 53325 AN: 145474 Hom.: 9650 Cov.: 25 AF XY: 0.378 AC XY: 26594 AN XY: 70416

African (AFR) AF: 0.387 AC: 15084 AN: 39012

American (AMR) AF: 0.434 AC: 6189 AN: 14262

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1267 AN: 3440

East Asian (EAS) AF: 0.407 AC: 2016 AN: 4948

South Asian (SAS) AF: 0.422 AC: 1952 AN: 4628

European-Finnish (FIN) AF: 0.474 AC: 4307 AN: 9094

Middle Eastern (MID) AF: 0.431 AC: 113 AN: 262

European-Non Finnish (NFE) AF: 0.317 AC: 21239 AN: 66914

Other (OTH) AF: 0.374 AC: 750 AN: 2008

Alfa AF: 0.330 Hom.: 21780

Bravo AF: 0.356

Asia WGS AF: 0.391 AC: 1356 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		-0.48
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: rs2857103; hg19: chr6-32791299;