6-32830099-A-G

Position:

chr6-32830099-A-G

Variant summary

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

The NM_001290043.2(TAP2):c.1636-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,612,616 control chromosomes in the GnomAD database, including 178,837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14915 hom., cov: 32)

Exomes 𝑓: 0.47 ( 163922 hom. )

Consequence

TAP2
NM_001290043.2 intron

Scores

Splicing: ADA: 0.0001206

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.0240

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-32830099-A-G is Benign according to our data. Variant chr6-32830099-A-G is described in ClinVar as [Benign]. Clinvar id is 403515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32830099-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.1636-10T>C		intron_variant		ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1636-10T>C		intron_variant			NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4 link	c.1636-10T>C		intron_variant		1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1636-10T>C		intron_variant		2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.430

AC:

65318

AN:

151936

Hom.:

14913

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.549

Gnomad SAS

AF:

0.498

Gnomad FIN

AF:

0.571

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.469

GnomAD3 exomes

AF:

0.490

AC:

120649

AN:

246450

Hom.:

30323

AF XY:

0.491

AC XY:

66023

AN XY:

134332

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.540

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.540

Gnomad SAS exome

AF:

0.505

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.469

Gnomad OTH exome

AF:

0.489

GnomAD4 exome

AF:

0.470

AC:

686261

AN:

1460562

Hom.:

163922

Cov.:

AF XY:

0.473

AC XY:

343457

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.531

Gnomad4 ASJ exome

AF:

0.593

Gnomad4 EAS exome

AF:

0.583

Gnomad4 SAS exome

AF:

0.508

Gnomad4 FIN exome

AF:

0.561

Gnomad4 NFE exome

AF:

0.459

Gnomad4 OTH exome

AF:

0.474

GnomAD4 genome

AF:

0.430

AC:

65338

AN:

152054

Hom.:

14915

Cov.:

AF XY:

0.436

AC XY:

32435

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.267

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.548

Gnomad4 SAS

AF:

0.496

Gnomad4 FIN

AF:

0.571

Gnomad4 NFE

AF:

0.471

Gnomad4 OTH

AF:

0.470

Alfa

AF:

0.464

Hom.:

22641

Bravo

AF:

0.414

Asia WGS

AF:

0.530

AC:

1844

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other: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	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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 -

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

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.5

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.016

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