6-32832787-G-C

Variant names:

• chr6-32832787-G-C
• rs148663600
• NM_001290043.2:c.983C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001290043.2(TAP2):​c.983C>G​(p.Ala328Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000539 in 1,612,810 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A328A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00063 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00053 (9 hom.)
• Consequence: TAP2 NM_001290043.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 3.52
• Publications: 3 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010731518).
• BP6: Variant 6-32832787-G-C is Benign according to our data. Variant chr6-32832787-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 534733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000631 (96/152212) while in subpopulation SAS AF = 0.0102 (49/4824). AF 95% confidence interval is 0.00789. There are 3 homozygotes in GnomAd4. There are 54 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.983C>G	p.Ala328Gly	missense	Exon 6 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.983C>G	p.Ala328Gly	missense	Exon 6 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.983C>G	p.Ala328Gly	missense	Exon 6 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.983C>G	p.Ala328Gly	missense	Exon 6 of 15	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.983C>G	p.Ala328Gly	missense	Exon 6 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.000631 AC: 96 AN: 152094 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00104 AC: 257 AN: 246388 AF XY: 0.00141

Gnomad AFR exome AF: 0.000331

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000530 AC: 774 AN: 1460598 Hom.: 9 Cov.: 35 AF XY: 0.000717 AC XY: 521 AN XY: 726634

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000856 AC: 34 AN: 39698

South Asian (SAS) AF: 0.00660 AC: 569 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52142

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1112008

Other (OTH) AF: 0.00242 AC: 146 AN: 60384

GnomAD4 genome AF: 0.000631 AC: 96 AN: 152212 Hom.: 3 Cov.: 32 AF XY: 0.000726 AC XY: 54 AN XY: 74428

African (AFR) AF: 0.000361 AC: 15 AN: 41534

American (AMR) AF: 0.000262 AC: 4 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00445 AC: 23 AN: 5172

South Asian (SAS) AF: 0.0102 AC: 49 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67998

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.000385

ExAC AF: 0.00116 AC: 137

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

MHC class I deficiency Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	0.17
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.011	T
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		3.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.010	D
Sift4G	Benign	0.068	T
Polyphen		0.13	B
Vest4		0.22
MVP		0.60
MPC		0.76
ClinPred		0.11	T
GERP RS		5.0
Varity_R		0.51
gMVP		0.74
Mutation Taster		=94/6	polymorphism

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: rs148663600; hg19: chr6-32800564;