rs241447

Variant names:

• chr6-32828974-T-C
• rs241447
• NM_001290043.2:c.1993A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32828974-T-C
• chr6-32828974-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001290043.2(TAP2):​c.1993A>G​(p.Thr665Ala) variant causes a missense change. The variant allele was found at a frequency of 0.269 in 1,549,446 control chromosomes in the GnomAD database, including 58,603 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5642 hom., cov: 30)
  • Exomes 𝑓: 0.27 (52961 hom.)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.70
• Publications: 103 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: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.031624883).
• BP6: Variant 6-32828974-T-C is Benign according to our data. Variant chr6-32828974-T-C is described in ClinVar as Benign. ClinVar VariationId is 403511.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.

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.1993A>G	p.Thr665Ala	missense	Exon 12 of 12	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1932+426A>G		intron	N/A	NP_061313.2	Q9UP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.1993A>G	p.Thr665Ala	missense	Exon 12 of 12	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+426A>G		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698449.1		c.2026A>G	p.Thr676Ala	missense	Exon 13 of 13	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40167 AN: 151784 Hom.: 5632 Cov.: 30

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.291

GnomAD2 exomes AF: 0.313 AC: 47971 AN: 153132 AF XY: 0.315

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.359

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.298

GnomAD4 exome AF: 0.269 AC: 376632 AN: 1397544 Hom.: 52961 Cov.: 43 AF XY: 0.273 AC XY: 188203 AN XY: 689444

African (AFR) AF: 0.184 AC: 5844 AN: 31716

American (AMR) AF: 0.347 AC: 12518 AN: 36028

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 8834 AN: 25274

East Asian (EAS) AF: 0.353 AC: 12682 AN: 35886

South Asian (SAS) AF: 0.393 AC: 31012 AN: 78988

European-Finnish (FIN) AF: 0.335 AC: 15679 AN: 46812

Middle Eastern (MID) AF: 0.297 AC: 1692 AN: 5694

European-Non Finnish (NFE) AF: 0.252 AC: 272114 AN: 1079122

Other (OTH) AF: 0.280 AC: 16257 AN: 58024

GnomAD4 genome AF: 0.265 AC: 40199 AN: 151902 Hom.: 5642 Cov.: 30 AF XY: 0.273 AC XY: 20265 AN XY: 74242

African (AFR) AF: 0.185 AC: 7661 AN: 41426

American (AMR) AF: 0.329 AC: 5028 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1194 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1886 AN: 5160

South Asian (SAS) AF: 0.399 AC: 1913 AN: 4800

European-Finnish (FIN) AF: 0.345 AC: 3631 AN: 10530

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.262 AC: 17829 AN: 67930

Other (OTH) AF: 0.292 AC: 616 AN: 2112

Alfa AF: 0.262 Hom.: 17280

Bravo AF: 0.259

TwinsUK AF: 0.230 AC: 851

ALSPAC AF: 0.239 AC: 921

ESP6500AA AF: 0.156 AC: 397

ESP6500EA AF: 0.214 AC: 1026

ExAC AF: 0.190 AC: 17273

Asia WGS AF: 0.365 AC: 1269 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	MHC class I deficiency (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.95	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.7
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.29
Sift	Benign	0.037	D
Sift4G	Uncertain	0.010	D
Polyphen		0.19	B
Vest4		0.082
ClinPred		0.042	T
GERP RS		3.4
Varity_R		0.067
gMVP		0.48
Mutation Taster		=97/3	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: rs241447; hg19: chr6-32796751; COSMIC: COSV66497946; COSMIC: COSV66497946;