6-32829973-G-A

Variant names:

• chr6-32829973-G-A
• rs144543918
• NM_001290043.2:c.1752C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001290043.2(TAP2):​c.1752C>T​(p.His584His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000337 in 1,613,056 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00097 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (0 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39
• Publications: 2 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-32829973-G-A is Benign according to our data. Variant chr6-32829973-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 466368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.39 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000972 (148/152274) while in subpopulation AFR AF = 0.000698 (29/41532). AF 95% confidence interval is 0.000499. There are 3 homozygotes in GnomAd4. There are 65 alleles in the male GnomAd4 subpopulation. Median coverage is 33. 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.1752C>T	p.His584His	synonymous	Exon 10 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.1752C>T	p.His584His	synonymous	Exon 10 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.1752C>T	p.His584His	synonymous	Exon 10 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1752C>T	p.His584His	synonymous	Exon 10 of 15	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.1785C>T	p.His595His	synonymous	Exon 11 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.000966 AC: 147 AN: 152156 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000227 AC: 56 AN: 246662 AF XY: 0.000201

Gnomad AFR exome AF: 0.000397

Gnomad AMR exome AF: 0.000406

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000307

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000271 AC: 396 AN: 1460782 Hom.: 0 Cov.: 67 AF XY: 0.000242 AC XY: 176 AN XY: 726702

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000382 AC: 2 AN: 52330

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000298 AC: 331 AN: 1112004

Other (OTH) AF: 0.000199 AC: 12 AN: 60384

GnomAD4 genome AF: 0.000972 AC: 148 AN: 152274 Hom.: 3 Cov.: 33 AF XY: 0.000873 AC XY: 65 AN XY: 74450

African (AFR) AF: 0.000698 AC: 29 AN: 41532

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000625 Hom.: 0

Bravo AF: 0.00120

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

MHC class I deficiency Benign:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TAP2: BP4, BP7

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.33
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144543918; hg19: chr6-32797750; COSMIC: COSV66501588; COSMIC: COSV66501588;