NM_001290043.2:c.1932+9C>T

Variant names:

• chr6-32829391-G-A
• rs241442
• NM_001290043.2:c.1932+9C>T

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.1932+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,586,668 control chromosomes in the GnomAD database, including 58,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5465 hom., cov: 31)
  • Exomes 𝑓: 0.27 (53416 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.878
• Publications: 17 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 (BayesDel_noAF=-0.81).
• BP6: Variant 6-32829391-G-A is Benign according to our data. Variant chr6-32829391-G-A is described in ClinVar as Benign. ClinVar VariationId is 403512.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.1932+9C>T		intron	N/A	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1932+9C>T		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.1932+9C>T		intron	N/A	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1932+9C>T		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698449.1		c.1965+9C>T		intron	N/A	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39662 AN: 151882 Hom.: 5455 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.289 AC: 60170 AN: 208310 AF XY: 0.294

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.286

GnomAD4 exome AF: 0.267 AC: 383734 AN: 1434668 Hom.: 53416 Cov.: 47 AF XY: 0.271 AC XY: 192733 AN XY: 710992

African (AFR) AF: 0.182 AC: 6011 AN: 33100

American (AMR) AF: 0.284 AC: 11423 AN: 40176

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 8907 AN: 25526

East Asian (EAS) AF: 0.350 AC: 13545 AN: 38716

South Asian (SAS) AF: 0.391 AC: 32347 AN: 82832

European-Finnish (FIN) AF: 0.337 AC: 17386 AN: 51538

Middle Eastern (MID) AF: 0.292 AC: 1606 AN: 5504

European-Non Finnish (NFE) AF: 0.251 AC: 275992 AN: 1097846

Other (OTH) AF: 0.278 AC: 16517 AN: 59430

GnomAD4 genome AF: 0.261 AC: 39693 AN: 152000 Hom.: 5465 Cov.: 31 AF XY: 0.269 AC XY: 19995 AN XY: 74286

African (AFR) AF: 0.183 AC: 7571 AN: 41474

American (AMR) AF: 0.306 AC: 4678 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3470

East Asian (EAS) AF: 0.358 AC: 1837 AN: 5128

South Asian (SAS) AF: 0.398 AC: 1920 AN: 4820

European-Finnish (FIN) AF: 0.344 AC: 3636 AN: 10560

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17813 AN: 67950

Other (OTH) AF: 0.287 AC: 607 AN: 2112

Alfa AF: 0.248 Hom.: 9772

Bravo AF: 0.253

Asia WGS AF: 0.363 AC: 1262 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.14
DANN	Benign	0.59
PhyloP100		-0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs241442; hg19: chr6-32797168; COSMIC: COSV66497927; COSMIC: COSV66497927;