6-32832800-C-T

Position:

chr6-32832800-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_001290043.2(TAP2):c.970G>A(p.Ala324Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000732 in 1,612,870 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00077 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 1 hom. )

Consequence

TAP2
NM_001290043.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.26

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:

ENSG00000250264 (HGNC:):

ENSG00000250264 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012103558).

BP6

Variant 6-32832800-C-T is Benign according to our data. Variant chr6-32832800-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 534728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32832800-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000768 (117/152356) while in subpopulation NFE AF= 0.00118 (80/68038). AF 95% confidence interval is 0.000967. There are 0 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2 linkuse as main transcript	c.970G>A	p.Ala324Thr	missense_variant	6/12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 linkuse as main transcript	c.970G>A	p.Ala324Thr	missense_variant	6/12		NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 linkuse as main transcript	c.970G>A	p.Ala324Thr	missense_variant	6/12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 linkuse as main transcript	c.970G>A	p.Ala324Thr	missense_variant	6/15	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.000769

AC:

117

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000650

AC:

160

AN:

246342

Hom.:

AF XY:

0.000730

AC XY:

AN XY:

134298

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000691

Gnomad FIN exome

AF:

0.00220

Gnomad NFE exome

AF:

0.000750

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000729

AC:

1064

AN:

1460514

Hom.:

Cov.:

AF XY:

0.000782

AC XY:

568

AN XY:

726590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000800

Gnomad4 FIN exome

AF:

0.00250

Gnomad4 NFE exome

AF:

0.000729

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000768

AC:

117

AN:

152356

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00263

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000712

Hom.:

Bravo

AF:

0.000450

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000663

AC:

ESP6500EA

AF:

0.000738

AC:

ExAC

AF:

0.000729

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00107

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

TAP2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;.;.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.81

T;.;.;.

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

1.6

.;L;.;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.2

N;N;.;N

REVEL

Uncertain

0.30

Sift

Benign

0.10

T;T;.;T

Sift4G

Benign

0.12

.;T;D;D

Polyphen

0.29

.;.;.;B

Vest4

0.13, 0.13

MVP

0.48

MPC

0.49

ClinPred

0.0086

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.70

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

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