6-32837616-T-C

Position:

• chr6-32837616-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001290043.2(TAP2):​c.529A>G​(p.Ile177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I177F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3149873).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.529A>G	p.Ile177Val	missense_variant	3/12	ENST00000374897.4
TAP2	NM_018833.3	c.529A>G	p.Ile177Val	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.529A>G	p.Ile177Val	missense_variant	3/12	1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;.;.;T
Eigen	Benign	0.081
Eigen_PC	Benign	0.083
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.79	T;.;.;.
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.8	.;M;.;M
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	-0.89	N;N;.;N
REVEL	Uncertain	0.38
Sift	Benign	0.13	T;D;.;D
Sift4G	Uncertain	0.026	.;D;D;D
Polyphen		0.51	.;.;.;P
Vest4		0.099, 0.096
MutPred		0.58		Gain of methylation at R175 (P = 0.102);Gain of methylation at R175 (P = 0.102);Gain of methylation at R175 (P = 0.102);Gain of methylation at R175 (P = 0.102);
MVP		0.40
MPC		0.78
ClinPred		0.86	D
GERP RS		2.0
Varity_R		0.12
gMVP		0.70

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

Other links and lift over

dbSNP: rs761121102; hg19: chr6-32805393;