rs1004855025

Variant names:

• chr6-32830761-C-A
• rs1004855025
• NM_001290043.2:c.1318G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32830761-C-A
• chr6-32830761-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001290043.2(TAP2):​c.1318G>T​(p.Ala440Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• MHC class I deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290043.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.1318G>T	p.Ala440Ser	missense	Exon 8 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.1318G>T	p.Ala440Ser	missense	Exon 8 of 12	NP_061313.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.1318G>T	p.Ala440Ser	missense	Exon 8 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1318G>T	p.Ala440Ser	missense	Exon 8 of 15	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.1351G>T	p.Ala451Ser	missense	Exon 9 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	MHC class I deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.40
Sift	Benign	0.62	T
Sift4G	Uncertain	0.054	T
Polyphen		1.0	D
Vest4		0.22
MutPred		0.60		Gain of disorder (P = 0.0257)
MVP		0.59
MPC		0.94
ClinPred		0.93	D
GERP RS		5.6
Varity_R		0.15
gMVP		0.61
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1004855025; hg19: chr6-32798538;