6-32835724-G-T

Variant names:

• chr6-32835724-G-T
• rs142794316
• NM_001290043.2:c.658C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001290043.2(TAP2):​c.658C>A​(p.Arg220Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,613,084 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (36 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.579
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 6-32835724-G-T is Benign according to our data. Variant chr6-32835724-G-T is described in ClinVar as Benign. ClinVar VariationId is 466374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.579 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0106 (1617/152266) while in subpopulation AFR AF = 0.0296 (1231/41534). AF 95% confidence interval is 0.0283. There are 27 homozygotes in GnomAd4. There are 806 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 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.658C>A	p.Arg220Arg	synonymous	Exon 4 of 12	NP_001276972.1
	TAP2	NM_018833.3		c.658C>A	p.Arg220Arg	synonymous	Exon 4 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.658C>A	p.Arg220Arg	synonymous	Exon 4 of 12	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.658C>A	p.Arg220Arg	synonymous	Exon 4 of 15	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.658C>A	p.Arg220Arg	synonymous	Exon 4 of 13	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1609 AN: 152148 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00203

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00483 AC: 1191 AN: 246666 AF XY: 0.00371

Gnomad AFR exome AF: 0.0286

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.000301

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00199

Gnomad OTH exome AF: 0.00872

GnomAD4 exome AF: 0.00270 AC: 3943 AN: 1460818 Hom.: 36 Cov.: 33 AF XY: 0.00251 AC XY: 1821 AN XY: 726728

African (AFR) AF: 0.0271 AC: 908 AN: 33480

American (AMR) AF: 0.0134 AC: 600 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.000290 AC: 25 AN: 86258

European-Finnish (FIN) AF: 0.000153 AC: 8 AN: 52358

Middle Eastern (MID) AF: 0.00659 AC: 38 AN: 5768

European-Non Finnish (NFE) AF: 0.00179 AC: 1986 AN: 1112008

Other (OTH) AF: 0.00614 AC: 371 AN: 60386

GnomAD4 genome AF: 0.0106 AC: 1617 AN: 152266 Hom.: 27 Cov.: 32 AF XY: 0.0108 AC XY: 806 AN XY: 74452

African (AFR) AF: 0.0296 AC: 1231 AN: 41534

American (AMR) AF: 0.0139 AC: 213 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00203 AC: 138 AN: 68024

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.00486 Hom.: 5

Bravo AF: 0.0129

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TAP2-related disorder Benign:1

Apr 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		0.58
Mutation Taster		=100/0	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: rs142794316; hg19: chr6-32803501;