6-32828908-A-G

Position:

chr6-32828908-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBA1

The NM_001290043.2(TAP2):c.2059T>C(p.Ter687GlnextTer17) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,543,082 control chromosomes in the GnomAD database, including 58,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. *687*) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.27 ( 5925 hom., cov: 30)

Exomes 𝑓: 0.27 ( 52954 hom. )

Consequence

TAP2
NM_001290043.2 stop_lost

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.36

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 -14 ACMG points.

PM4

Stoplost variant in NM_001290043.2 Downstream stopcodon found after 42 codons.

BP6

Variant 6-32828908-A-G is Benign according to our data. Variant chr6-32828908-A-G is described in ClinVar as [Benign]. Clinvar id is 403510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32828908-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2 linkuse as main transcript	c.2059T>C	p.Ter687GlnextTer17	stop_lost	12/12	ENST00000374897.4
TAP2	NM_018833.3 linkuse as main transcript	c.1932+492T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4 linkuse as main transcript	c.2059T>C	p.Ter687GlnextTer17	stop_lost	12/12	1	NM_001290043.2	A2	Q03519-1

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41592

AN:

151740

Hom.:

5915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.367

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.316

AC:

47140

AN:

148998

Hom.:

7808

AF XY:

0.318

AC XY:

25415

AN XY:

80040

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.361

Gnomad SAS exome

AF:

0.394

Gnomad FIN exome

AF:

0.343

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.270

AC:

376064

AN:

1391224

Hom.:

52954

Cov.:

AF XY:

0.274

AC XY:

187494

AN XY:

685394

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.349

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.274

AC:

41625

AN:

151858

Hom.:

5925

Cov.:

AF XY:

0.282

AC XY:

20934

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.367

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.273

Hom.:

8801

Bravo

AF:

0.270

TwinsUK

AF:

0.225

AC:

833

ALSPAC

AF:

0.238

AC:

919

ESP6500AA

AF:

0.161

AC:

385

ESP6500EA

AF:

0.190

AC:

895

ExAC

AF:

0.145

AC:

11752

Asia WGS

AF:

0.366

AC:

1274

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Mendelics	May 28, 2019	- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.019

DANN

Benign

0.32

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.014

GERP RS

-12

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