chr6-32828947-C-T

Position:

chr6-32828947-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001290043.2(TAP2):c.2020G>A(p.Val674Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000672 in 1,546,868 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000065 ( 1 hom. )

Consequence

TAP2
NM_001290043.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4219219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2 linkuse as main transcript	c.2020G>A	p.Val674Met	missense_variant	12/12	ENST00000374897.4
TAP2	NM_018833.3 linkuse as main transcript	c.1932+453G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4 linkuse as main transcript	c.2020G>A	p.Val674Met	missense_variant	12/12	1	NM_001290043.2	A2	Q03519-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000864

AC:

AN:

150512

Hom.:

AF XY:

0.0000618

AC XY:

AN XY:

80948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000809

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000353

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000645

AC:

AN:

1394728

Hom.:

Cov.:

AF XY:

0.0000611

AC XY:

AN XY:

687778

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000838

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000356

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000482

Gnomad4 OTH exome

AF:

0.0000863

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000103

Hom.:

Bravo

AF:

0.000147

ExAC

AF:

0.000104

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class I deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Nov 01, 2022

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 674 of the TAP2 protein (p.Val674Met). This variant is present in population databases (rs763950001, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1044539). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

.;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.42

T;T

MetaSVM

Uncertain

0.58

MutationAssessor

Uncertain

2.7

.;M

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.0

.;N

REVEL

Pathogenic

0.70

Sift

Uncertain

0.0080

.;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

.;D

Vest4

0.41

MutPred

0.83

Gain of disorder (P = 0.0818);Gain of disorder (P = 0.0818);

MVP

0.90

ClinPred

0.29

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.050

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over