6-32830099-A-G

Variant names:

• chr6-32830099-A-G
• rs241436
• NM_001290043.2:c.1636-10T>C

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.1636-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,612,616 control chromosomes in the GnomAD database, including 178,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (14915 hom., cov: 32)
  • Exomes 𝑓: 0.47 (163922 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Scores: Splicing: ADA: 0.0001206
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.0240
• Publications: 45 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-32830099-A-G is Benign according to our data. Variant chr6-32830099-A-G is described in ClinVar as Benign. ClinVar VariationId is 403515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 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.1636-10T>C		intron	N/A	NP_001276972.1
	TAP2	NM_018833.3		c.1636-10T>C		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.1636-10T>C		intron	N/A	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1636-10T>C		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.1669-10T>C		intron	N/A	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65318 AN: 151936 Hom.: 14913 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.469

GnomAD2 exomes AF: 0.490 AC: 120649 AN: 246450 AF XY: 0.491

Gnomad AFR exome AF: 0.261

Gnomad AMR exome AF: 0.540

Gnomad ASJ exome AF: 0.594

Gnomad EAS exome AF: 0.540

Gnomad FIN exome AF: 0.560

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.489

GnomAD4 exome AF: 0.470 AC: 686261 AN: 1460562 Hom.: 163922 Cov.: 65 AF XY: 0.473 AC XY: 343457 AN XY: 726596

African (AFR) AF: 0.260 AC: 8719 AN: 33478

American (AMR) AF: 0.531 AC: 23740 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 15505 AN: 26136

East Asian (EAS) AF: 0.583 AC: 23143 AN: 39700

South Asian (SAS) AF: 0.508 AC: 43787 AN: 86244

European-Finnish (FIN) AF: 0.561 AC: 29336 AN: 52336

Middle Eastern (MID) AF: 0.529 AC: 2985 AN: 5648

European-Non Finnish (NFE) AF: 0.459 AC: 510423 AN: 1111932

Other (OTH) AF: 0.474 AC: 28623 AN: 60364

GnomAD4 genome AF: 0.430 AC: 65338 AN: 152054 Hom.: 14915 Cov.: 32 AF XY: 0.436 AC XY: 32435 AN XY: 74336

African (AFR) AF: 0.267 AC: 11091 AN: 41484

American (AMR) AF: 0.488 AC: 7466 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2010 AN: 3464

East Asian (EAS) AF: 0.548 AC: 2831 AN: 5162

South Asian (SAS) AF: 0.496 AC: 2391 AN: 4816

European-Finnish (FIN) AF: 0.571 AC: 6032 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 31973 AN: 67948

Other (OTH) AF: 0.470 AC: 992 AN: 2112

Alfa AF: 0.456 Hom.: 56905

Bravo AF: 0.414

Asia WGS AF: 0.530 AC: 1844 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.45
PhyloP100		-0.024
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.016
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: rs241436; hg19: chr6-32797876; COSMIC: COSV66498026; COSMIC: COSV66498026;