rs2856992

Variant names:

• chr6-32832444-C-T
• rs2856992
• NM_001290043.2:c.1161G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001290043.2(TAP2):​c.1161G>A​(p.Val387Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,612,722 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (46 hom., cov: 32)
  • Exomes 𝑓: 0.024 (524 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.65

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 6-32832444-C-T is Benign according to our data. Variant chr6-32832444-C-T is described in ClinVar as [Benign]. Clinvar id is 466365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0204 (3105/152320) while in subpopulation AMR AF= 0.0283 (433/15302). AF 95% confidence interval is 0.0261. There are 46 homozygotes in gnomad4. There are 1378 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 12	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.1161G>A	p.Val387Val	synonymous_variant	Exon 7 of 15	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3104 AN: 152202 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0301

GnomAD3 exomes AF: 0.0145 AC: 3561 AN: 245660 Hom.: 45 AF XY: 0.0139 AC XY: 1863 AN XY: 133854

Gnomad AFR exome AF: 0.0207

Gnomad AMR exome AF: 0.0182

Gnomad ASJ exome AF: 0.00673

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000991

Gnomad FIN exome AF: 0.00315

Gnomad NFE exome AF: 0.0215

Gnomad OTH exome AF: 0.0192

GnomAD4 exome AF: 0.0242 AC: 35398 AN: 1460402 Hom.: 524 Cov.: 32 AF XY: 0.0230 AC XY: 16727 AN XY: 726462

Gnomad4 AFR exome AF: 0.0209

Gnomad4 AMR exome AF: 0.0197

Gnomad4 ASJ exome AF: 0.00750

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00354

Gnomad4 NFE exome AF: 0.0288

Gnomad4 OTH exome AF: 0.0220

GnomAD4 genome AF: 0.0204 AC: 3105 AN: 152320 Hom.: 46 Cov.: 32 AF XY: 0.0185 AC XY: 1378 AN XY: 74494

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.0283

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.0298

Alfa AF: 0.0198 Hom.: 38

Bravo AF: 0.0233

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.0234

EpiControl AF: 0.0234

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TAP2-related disorder Benign:1

May 09, 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	5.9
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2856992; hg19: chr6-32800221;