NM_001290043.2:c.2059T>C

Variant names:

• chr6-32828908-A-G
• rs241448
• NM_001290043.2:c.2059T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The NM_001290043.2(TAP2):​c.2059T>C​(p.Ter687Glnext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,543,082 control chromosomes in the GnomAD database, including 58,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (5925 hom., cov: 30)
  • Exomes 𝑓: 0.27 (52954 hom.)
• Consequence: TAP2 NM_001290043.2 stop_lost
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.36
• Publications: 81 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.

• PM4: Stoplost variant in NM_001290043.2 Downstream stopcodon found after 34 codons.
• BP6: Variant 6-32828908-A-G is Benign according to our data. Variant chr6-32828908-A-G is described in ClinVar as Benign. ClinVar VariationId is 403510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.2059T>C	p.Ter687Glnext*?	stop_lost	Exon 12 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1932+492T>C		intron_variant	Intron 11 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.2059T>C	p.Ter687Glnext*?	stop_lost	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1932+492T>C		intron_variant	Intron 11 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41592 AN: 151740 Hom.: 5915 Cov.: 30

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.316 AC: 47140 AN: 148998 AF XY: 0.318

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.361

Gnomad FIN exome AF: 0.343

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.270 AC: 376064 AN: 1391224 Hom.: 52954 Cov.: 39 AF XY: 0.274 AC XY: 187494 AN XY: 685394

African (AFR) AF: 0.218 AC: 6892 AN: 31566

American (AMR) AF: 0.349 AC: 12483 AN: 35728

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 8784 AN: 25172

East Asian (EAS) AF: 0.354 AC: 12598 AN: 35636

South Asian (SAS) AF: 0.393 AC: 30817 AN: 78388

European-Finnish (FIN) AF: 0.335 AC: 15387 AN: 45872

Middle Eastern (MID) AF: 0.298 AC: 1675 AN: 5624

European-Non Finnish (NFE) AF: 0.252 AC: 271164 AN: 1075496

Other (OTH) AF: 0.282 AC: 16264 AN: 57742

GnomAD4 genome AF: 0.274 AC: 41625 AN: 151858 Hom.: 5925 Cov.: 30 AF XY: 0.282 AC XY: 20934 AN XY: 74220

African (AFR) AF: 0.217 AC: 8974 AN: 41404

American (AMR) AF: 0.334 AC: 5101 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1195 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1884 AN: 5140

South Asian (SAS) AF: 0.399 AC: 1916 AN: 4806

European-Finnish (FIN) AF: 0.345 AC: 3634 AN: 10544

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

European-Non Finnish (NFE) AF: 0.263 AC: 17856 AN: 67892

Other (OTH) AF: 0.296 AC: 625 AN: 2110

Alfa AF: 0.274 Hom.: 13234

Bravo AF: 0.270

TwinsUK AF: 0.225 AC: 833

ALSPAC AF: 0.238 AC: 919

ESP6500AA AF: 0.161 AC: 385

ESP6500EA AF: 0.190 AC: 895

ExAC AF: 0.145 AC: 11752

Asia WGS AF: 0.366 AC: 1274 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

MHC class I deficiency Benign:2

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.019
DANN	Benign	0.32
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
PhyloP100		-1.4
GERP RS		-12
Mutation Taster		=160/40	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: rs241448; hg19: chr6-32796685; COSMIC: COSV66498061; COSMIC: COSV66498061;