rs2228396

Positions:

• chr6-32830032-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001290043.2(TAP2):​c.1693G>A​(p.Ala565Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 1,613,076 control chromosomes in the GnomAD database, including 7,097 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.092 (724 hom., cov: 33)
  • Exomes 𝑓: 0.089 (6373 hom.)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.638

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]

ENSG00000250264 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003592223).
• BP6: Variant 6-32830032-C-T is Benign according to our data. Variant chr6-32830032-C-T is described in ClinVar as [Benign]. Clinvar id is 1168813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.1693G>A	p.Ala565Thr	missense_variant	10/12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1693G>A	p.Ala565Thr	missense_variant	10/12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.1693G>A	p.Ala565Thr	missense_variant	10/12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1693G>A	p.Ala565Thr	missense_variant	10/15	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13940 AN: 152142 Hom.: 722 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0782

Gnomad ASJ AF: 0.0499

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0871

Gnomad OTH AF: 0.0655

GnomAD3 exomes AF: 0.0800 AC: 19729 AN: 246668 Hom.: 930 AF XY: 0.0749 AC XY: 10063 AN XY: 134434

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.0908

Gnomad ASJ exome AF: 0.0490

Gnomad EAS exome AF: 0.104

Gnomad SAS exome AF: 0.0212

Gnomad FIN exome AF: 0.0790

Gnomad NFE exome AF: 0.0869

Gnomad OTH exome AF: 0.0734

GnomAD4 exome AF: 0.0892 AC: 130356 AN: 1460816 Hom.: 6373 Cov.: 72 AF XY: 0.0862 AC XY: 62679 AN XY: 726718

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.0503

Gnomad4 EAS exome AF: 0.0871

Gnomad4 SAS exome AF: 0.0219

Gnomad4 FIN exome AF: 0.0787

Gnomad4 NFE exome AF: 0.0956

Gnomad4 OTH exome AF: 0.0861

GnomAD4 genome AF: 0.0918 AC: 13976 AN: 152260 Hom.: 724 Cov.: 33 AF XY: 0.0896 AC XY: 6671 AN XY: 74454

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0782

Gnomad4 ASJ AF: 0.0499

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0874 Hom.: 1051

Bravo AF: 0.0953

TwinsUK AF: 0.109 AC: 406

ALSPAC AF: 0.108 AC: 416

ESP6500AA AF: 0.122 AC: 368

ESP6500EA AF: 0.0849 AC: 460

ExAC AF: 0.0792 AC: 9375

Asia WGS AF: 0.0790 AC: 276 AN: 3478

EpiCase AF: 0.0755

EpiControl AF: 0.0794

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	1.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;.;.;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.57	T;.;.;.
MetaRNN	Benign	0.0036	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.2	.;L;.;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N;N;.;N
REVEL	Benign	0.16
Sift	Benign	0.23	T;T;.;T
Sift4G	Benign	0.39	.;T;T;T
Polyphen		0.39	.;.;.;B
Vest4		0.017, 0.018
MPC		0.46
ClinPred		0.0046	T
GERP RS		1.5
Varity_R		0.044
gMVP		0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2228396; hg19: chr6-32797809; COSMIC: COSV66498340; COSMIC: COSV66498340;