6-32828188-G-A

Variant names:

• chr6-32828188-G-A
• rs241456
• NM_001290043.2:c.*718C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001290043.2(TAP2):​c.*718C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 882,234 control chromosomes in the GnomAD database, including 25,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5620 hom., cov: 31)
  • Exomes 𝑓: 0.23 (20188 hom.)
• Consequence: TAP2 NM_001290043.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280
• Publications: 38 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-32828188-G-A is Benign according to our data. Variant chr6-32828188-G-A is described in ClinVar as Benign. ClinVar VariationId is 1296950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.*718C>T		3_prime_UTR	Exon 12 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.1932+1212C>T		intron	N/A	NP_061313.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.*718C>T		3_prime_UTR	Exon 12 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+1212C>T		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000698440.1		c.*718C>T		3_prime_UTR	Exon 13 of 13	ENSP00000513722.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40110 AN: 151818 Hom.: 5610 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.233 AC: 169982 AN: 730298 Hom.: 20188 Cov.: 10 AF XY: 0.233 AC XY: 79046 AN XY: 339152

African (AFR) AF: 0.168 AC: 2329 AN: 13870

American (AMR) AF: 0.295 AC: 247 AN: 836

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1432 AN: 4410

East Asian (EAS) AF: 0.333 AC: 1029 AN: 3094

South Asian (SAS) AF: 0.388 AC: 5401 AN: 13934

European-Finnish (FIN) AF: 0.324 AC: 77 AN: 238

Middle Eastern (MID) AF: 0.261 AC: 364 AN: 1392

European-Non Finnish (NFE) AF: 0.229 AC: 153226 AN: 668600

Other (OTH) AF: 0.246 AC: 5877 AN: 23924

GnomAD4 genome AF: 0.264 AC: 40144 AN: 151936 Hom.: 5620 Cov.: 31 AF XY: 0.273 AC XY: 20239 AN XY: 74230

African (AFR) AF: 0.184 AC: 7606 AN: 41440

American (AMR) AF: 0.328 AC: 5013 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3466

East Asian (EAS) AF: 0.362 AC: 1865 AN: 5146

South Asian (SAS) AF: 0.399 AC: 1924 AN: 4824

European-Finnish (FIN) AF: 0.346 AC: 3647 AN: 10540

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17843 AN: 67936

Other (OTH) AF: 0.289 AC: 612 AN: 2114

Alfa AF: 0.259 Hom.: 20589

Bravo AF: 0.258

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29205500)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		0.028
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: rs241456; hg19: chr6-32795965;