rs55827768

chr6-32838190-A-Cchr6-32838190-A-G

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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]

ACMG classification

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/exons	MANE	UniProt
TAP2	NM_001290043.2	c.44T>G	p.Val15Gly	missense_variant	2/12	ENST00000374897.4
TAP2	NM_018833.3	c.44T>G	p.Val15Gly	missense_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.44T>G	p.Val15Gly	missense_variant	2/12	1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD3 exomes AF: 0.00000432 AC: 1 AN: 231482 Hom.: 0 AF XY: 0.00000794 AC XY: 1 AN XY: 126020

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: 1 AN: 1442202 Hom.: 0 Cov.: 35 AF XY: 0.00000140 AC XY: 1 AN XY: 715768

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.: 27

ExAC AF: 0.00000844 AC: 1

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	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Benign	16
Dann	Benign	0.81
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.72	T;.;.;.
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.57	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	D;D;.;D
REVEL	Uncertain	0.49
Sift	Pathogenic	0.0	D;D;.;D
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	T
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

Other links and lift over

dbSNP: rs55827768; hg19: chr6-32805967;