6-32835539-A-G

Variant names:

• chr6-32835539-A-G
• rs4148871
• NM_001290043.2:c.739+104T>C

Variant summary

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

The NM_001290043.2(TAP2):​c.739+104T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 1,553,386 control chromosomes in the GnomAD database, including 495,783 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 0.82 (51341 hom., cov: 31)
  • Exomes 𝑓: 0.80 (444442 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 28 publications found

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]

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

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290043.2. 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_001290043.2	MANE Select	c.739+104T>C		intron	N/A	NP_001276972.1
	TAP2	NM_018833.3		c.739+104T>C		intron	N/A	NP_061313.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.739+104T>C		intron	N/A	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.739+104T>C		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.739+104T>C		intron	N/A	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124740 AN: 151948 Hom.: 51283 Cov.: 31

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.896

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.804

GnomAD4 exome AF: 0.796 AC: 1114975 AN: 1401320 Hom.: 444442 Cov.: 24 AF XY: 0.794 AC XY: 554543 AN XY: 698438

African (AFR) AF: 0.858 AC: 27645 AN: 32222

American (AMR) AF: 0.811 AC: 33288 AN: 41056

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 19965 AN: 25586

East Asian (EAS) AF: 0.865 AC: 33828 AN: 39088

South Asian (SAS) AF: 0.743 AC: 62068 AN: 83544

European-Finnish (FIN) AF: 0.857 AC: 43962 AN: 51278

Middle Eastern (MID) AF: 0.720 AC: 3889 AN: 5404

European-Non Finnish (NFE) AF: 0.793 AC: 844006 AN: 1064696

Other (OTH) AF: 0.793 AC: 46324 AN: 58446

GnomAD4 genome AF: 0.821 AC: 124859 AN: 152066 Hom.: 51341 Cov.: 31 AF XY: 0.822 AC XY: 61141 AN XY: 74348

African (AFR) AF: 0.859 AC: 35618 AN: 41446

American (AMR) AF: 0.799 AC: 12211 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2736 AN: 3472

East Asian (EAS) AF: 0.896 AC: 4630 AN: 5168

South Asian (SAS) AF: 0.752 AC: 3617 AN: 4810

European-Finnish (FIN) AF: 0.874 AC: 9266 AN: 10600

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.796 AC: 54099 AN: 67982

Other (OTH) AF: 0.807 AC: 1699 AN: 2106

Alfa AF: 0.803 Hom.: 204370

Bravo AF: 0.819

Asia WGS AF: 0.835 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.52
PhyloP100		-0.25
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: rs4148871; hg19: chr6-32803316;