NM_001290043.2:c.1800A>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001290043.2(TAP2):c.1800A>C(p.Val600Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 1,613,994 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 387 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2070 hom. )

Consequence

TAP2
NM_001290043.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.01

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 6-32829532-T-G is Benign according to our data. Variant chr6-32829532-T-G is described in ClinVar as [Benign]. Clinvar id is 403514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1800A>C	p.Val600Val	synonymous_variant	Exon 11 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1800A>C	p.Val600Val	synonymous_variant	Exon 11 of 12		NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1800A>C	p.Val600Val	synonymous_variant	Exon 11 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1800A>C	p.Val600Val	synonymous_variant	Exon 11 of 15	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9766

AN:

152078

Hom.:

387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0395

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0397

GnomAD3 exomes

AF:

0.0510

AC:

12810

AN:

251306

Hom.:

440

AF XY:

0.0497

AC XY:

6744

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0268

Gnomad ASJ exome

AF:

0.0289

Gnomad EAS exome

AF:

0.0319

Gnomad SAS exome

AF:

0.0115

Gnomad FIN exome

AF:

0.0987

Gnomad NFE exome

AF:

0.0575

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0494

AC:

72185

AN:

1461798

Hom.:

2070

Cov.:

AF XY:

0.0483

AC XY:

35119

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0283

Gnomad4 ASJ exome

AF:

0.0295

Gnomad4 EAS exome

AF:

0.0468

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.0981

Gnomad4 NFE exome

AF:

0.0502

Gnomad4 OTH exome

AF:

0.0433

GnomAD4 genome

AF:

0.0642

AC:

9769

AN:

152196

Hom.:

387

Cov.:

AF XY:

0.0654

AC XY:

4863

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0997

Gnomad4 AMR

AF:

0.0394

Gnomad4 ASJ

AF:

0.0288

Gnomad4 EAS

AF:

0.0350

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0508

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0493

Hom.:

262

Bravo

AF:

0.0612

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0510

EpiControl

AF:

0.0501

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

MHC class I deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TAP2-related disorder

Benign:1

Jul 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.18

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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