dbSNP rs55827768: TAP2:p.Val15Gly (chr6-32838190-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001290043.2(TAP2):c.44T>G(p.Val15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V15A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TAP2
NM_001290043.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2 link	c.44T>G	p.Val15Gly	missense_variant	Exon 2 of 12	ENST00000374897.4	NP_001276972.1	Q03519-1Q5JNW1
TAP2	NM_018833.3 link	c.44T>G	p.Val15Gly	missense_variant	Exon 2 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.44T>G	p.Val15Gly	missense_variant	Exon 2 of 12	1	NM_001290043.2	ENSP00000364032.3		Q03519-1
ENSG00000250264	ENST00000452392.2 link	c.44T>G	p.Val15Gly	missense_variant	Exon 2 of 15	2		ENSP00000391806.2		E7ENX8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000432

AC:

AN:

231482

Hom.:

AF XY:

0.00000794

AC XY:

AN XY:

126020

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000964

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442202

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

715768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000844

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.14

.;.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.72

T;.;.;.

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.1

.;L;.;L

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.5

D;D;.;D

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;D;.;D

Sift4G

Benign

0.13

.;T;T;T

Polyphen

0.0

.;.;.;B

Vest4

0.26, 0.26, 0.27

MutPred

0.51

Loss of stability (P = 0.0018);Loss of stability (P = 0.0018);Loss of stability (P = 0.0018);Loss of stability (P = 0.0018);

MVP

0.38

MPC

0.59

ClinPred

0.15

GERP RS

-7.0

Varity_R

0.069

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: 47

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over