NM_001290043.2:c.162G>A

Variant names:

• chr6-32838072-C-T
• rs56064400
• NM_001290043.2:c.162G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001290043.2(TAP2):​c.162G>A​(p.Lys54Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,612,354 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (13 hom., cov: 28)
  • Exomes 𝑓: 0.0020 (93 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0620
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-32838072-C-T is Benign according to our data. Variant chr6-32838072-C-T is described in ClinVar as Benign. ClinVar VariationId is 534726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.062 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0667 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.162G>A	p.Lys54Lys	synonymous	Exon 2 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.162G>A	p.Lys54Lys	synonymous	Exon 2 of 12	NP_061313.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.162G>A	p.Lys54Lys	synonymous	Exon 2 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.162G>A	p.Lys54Lys	synonymous	Exon 2 of 15	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.162G>A	p.Lys54Lys	synonymous	Exon 2 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 411 AN: 151662 Hom.: 13 Cov.: 28

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0726

Gnomad SAS AF: 0.00482

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00337

GnomAD2 exomes AF: 0.00604 AC: 1488 AN: 246198 AF XY: 0.00573

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0771

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000362

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00203 AC: 2965 AN: 1460574 Hom.: 93 Cov.: 35 AF XY: 0.00200 AC XY: 1456 AN XY: 726552

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0648 AC: 2574 AN: 39700

South Asian (SAS) AF: 0.00208 AC: 179 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52400

Middle Eastern (MID) AF: 0.000707 AC: 4 AN: 5654

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111894

Other (OTH) AF: 0.00320 AC: 193 AN: 60342

GnomAD4 genome AF: 0.00271 AC: 411 AN: 151780 Hom.: 13 Cov.: 28 AF XY: 0.00330 AC XY: 245 AN XY: 74152

African (AFR) AF: 0.0000242 AC: 1 AN: 41358

American (AMR) AF: 0.000197 AC: 3 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0728 AC: 375 AN: 5154

South Asian (SAS) AF: 0.00482 AC: 23 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67904

Other (OTH) AF: 0.00333 AC: 7 AN: 2102

Alfa AF: 0.00139 Hom.: 4

Bravo AF: 0.00278

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class I deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		0.062
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: rs56064400; hg19: chr6-32805849; COSMIC: COSV66487871; COSMIC: COSV66487871;