rs111033561

Variant names:

• chr6-32828974-T-G
• rs241447
• NM_001290043.2:c.1993A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32828974-T-G
• chrNT_167244.2-4133840-C-G
• chrNT_113891.3-4241174-T-G
• chrNT_167245.2-4072545-C-G
• chrNT_167246.2-4248326-T-G
• chrNT_167247.2-4128054-T-G
• chrNT_167248.2-4023261-T-G
• chrNT_167249.2-4228228-C-G
• chrNT_167244.2-4133840-C-T
• chrNT_167245.2-4072545-C-T
• chrNT_167249.2-4228228-C-T
• chr6-32828974-T-C
• chrNT_113891.3-4241174-T-C
• chrNT_167246.2-4248326-T-C
• chrNT_167247.2-4128054-T-C
• chrNT_167248.2-4023261-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001290043.2(TAP2):​c.1993A>C​(p.Thr665Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T665A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70

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]

ENSG00000250264 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.1993A>C	p.Thr665Pro	missense_variant	Exon 12 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1932+426A>C		intron_variant	Intron 11 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.1993A>C	p.Thr665Pro	missense_variant	Exon 12 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1932+426A>C		intron_variant	Intron 11 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Uncertain	0.42	.;T
Eigen	Benign	0.060
Eigen_PC	Benign	-0.049
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.6	.;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.99	.;D
Vest4		0.55
MutPred		0.73		Loss of phosphorylation at T665 (P = 0.0433);Loss of phosphorylation at T665 (P = 0.0433);
MVP		0.87
ClinPred		0.97	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.24
gMVP		0.83

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: rs241447; hg19: chr6-32796751;