6-32832635-C-T

Position:

chr6-32832635-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001290043.2(TAP2):c.1135G>A(p.Val379Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,612,908 control chromosomes in the GnomAD database, including 16,466 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1653 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14813 hom. )

Consequence

TAP2
NM_001290043.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -2.53

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002161771).

BP6

Variant 6-32832635-C-T is Benign according to our data. Variant chr6-32832635-C-T is described in ClinVar as [Benign]. Clinvar id is 13724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32832635-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2 linkuse as main transcript	c.1135G>A	p.Val379Ile	missense_variant	6/12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3 linkuse as main transcript	c.1135G>A	p.Val379Ile	missense_variant	6/12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 linkuse as main transcript	c.1135G>A	p.Val379Ile	missense_variant	6/12	1	NM_001290043.2	ENSP00000364032	A2	Q03519-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21865

AN:

152028

Hom.:

1650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.0895

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.144

AC:

35501

AN:

246610

Hom.:

2695

AF XY:

0.140

AC XY:

18796

AN XY:

134420

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.168

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.0873

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.140

AC:

204942

AN:

1460762

Hom.:

14813

Cov.:

AF XY:

0.139

AC XY:

100866

AN XY:

726696

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.0904

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.144

AC:

21888

AN:

152146

Hom.:

1653

Cov.:

AF XY:

0.144

AC XY:

10704

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.0889

Gnomad4 FIN

AF:

0.146

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.142

Hom.:

3404

Bravo

AF:

0.146

TwinsUK

AF:

0.146

AC:

543

ALSPAC

AF:

0.145

AC:

557

ESP6500AA

AF:

0.149

AC:

450

ESP6500EA

AF:

0.137

AC:

742

ExAC

AF:

0.142

AC:

16766

Asia WGS

AF:

0.164

AC:

572

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.152

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class I deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

PEPTIDE TRANSPORTER PSF2 POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

May 01, 1992

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.0020

DANN

Benign

0.74

DEOGEN2

Benign

0.14

.;.;.;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.44

T;.;.;.

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.34

.;N;.;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.23

N;N;.;N

REVEL

Benign

0.20

Sift

Benign

0.49

T;T;.;T

Sift4G

Benign

0.85

.;T;T;T

Polyphen

0.029

.;.;.;B

Vest4

0.070, 0.071

MPC

0.37

ClinPred

0.0078

GERP RS

-9.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.014

gMVP

0.11

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