6-32829532-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001290043.2(TAP2):c.1800A>C(p.Val600=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0508 in 1,613,994 control chromosomes in the GnomAD database, including 2,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (387 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2070 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -5.01

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 6-32829532-T-G is Benign according to our data. Variant chr6-32829532-T-G is described in ClinVar as [Benign]. Clinvar id is 403514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.1800A>C	p.Val600=	synonymous_variant	11/12	ENST00000374897.4
TAP2	NM_018833.3	c.1800A>C	p.Val600=	synonymous_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.1800A>C	p.Val600=	synonymous_variant	11/12	1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9766 AN: 152078 Hom.: 387 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0397

GnomAD3 exomes AF: 0.0510 AC: 12810 AN: 251306 Hom.: 440 AF XY: 0.0497 AC XY: 6744 AN XY: 135830

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0268

Gnomad ASJ exome AF: 0.0289

Gnomad EAS exome AF: 0.0319

Gnomad SAS exome AF: 0.0115

Gnomad FIN exome AF: 0.0987

Gnomad NFE exome AF: 0.0575

Gnomad OTH exome AF: 0.0510

GnomAD4 exome AF: 0.0494 AC: 72185 AN: 1461798 Hom.: 2070 Cov.: 39 AF XY: 0.0483 AC XY: 35119 AN XY: 727206

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0283

Gnomad4 ASJ exome AF: 0.0295

Gnomad4 EAS exome AF: 0.0468

Gnomad4 SAS exome AF: 0.0119

Gnomad4 FIN exome AF: 0.0981

Gnomad4 NFE exome AF: 0.0502

Gnomad4 OTH exome AF: 0.0433

GnomAD4 genome AF: 0.0642 AC: 9769 AN: 152196 Hom.: 387 Cov.: 32 AF XY: 0.0654 AC XY: 4863 AN XY: 74404

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.0350

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0493 Hom.: 262

Bravo AF: 0.0612

Asia WGS AF: 0.0260 AC: 93 AN: 3478

EpiCase AF: 0.0510

EpiControl AF: 0.0501

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

MHC class I deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

TAP2-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 08, 2019

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	-0.71
Cadd	Benign	0.18
Dann	Benign	0.61
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: rs2229527; hg19: chr6-32797309;