Genetic Variant TAP2:c.*718C>T (chr6-32828188-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001290043.2(TAP2):c.*718C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 882,234 control chromosomes in the GnomAD database, including 25,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 5620 hom., cov: 31)

Exomes 𝑓: 0.23 ( 20188 hom. )

Consequence

TAP2
NM_001290043.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0280

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 6-32828188-G-A is Benign according to our data. Variant chr6-32828188-G-A is described in ClinVar as [Benign]. Clinvar id is 1296950.Status of the report is criteria_provided_single_submitter, 1 stars.

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 rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.*718C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.1932+1212C>T		intron_variant	Intron 11 of 11		NP_061313.2	Q03519-2Q9UP03

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897 link	c.*718C>T		3_prime_UTR_variant	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.1932+1212C>T		intron_variant	Intron 11 of 14	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40110

AN:

151818

Hom.:

5610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.399

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.289

GnomAD4 exome

AF:

0.233

AC:

169982

AN:

730298

Hom.:

20188

Cov.:

AF XY:

0.233

AC XY:

79046

AN XY:

339152

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.325

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.324

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.246

GnomAD4 genome

AF:

0.264

AC:

40144

AN:

151936

Hom.:

5620

Cov.:

AF XY:

0.273

AC XY:

20239

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.328

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.362

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.346

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.267

Hom.:

8021

Bravo

AF:

0.258

Asia WGS

AF:

0.357

AC:

1243

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29205500) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

DANN

Benign

0.66

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