rs1042116

Positions:

• chr6-32830771-G-A

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.1308C>T​(p.Asn436=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,612,240 control chromosomes in the GnomAD database, including 9,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (691 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8423 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.10

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=-0.62).
• BP6: Variant 6-32830771-G-A is Benign according to our data. Variant chr6-32830771-G-A is described in ClinVar as [Benign]. Clinvar id is 403516.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32830771-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-2.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.1308C>T	p.Asn436=	synonymous_variant	8/12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1308C>T	p.Asn436=	synonymous_variant	8/12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.1308C>T	p.Asn436=	synonymous_variant	8/12	1	NM_001290043.2	ENSP00000364032	A2

Frequencies

GnomAD3 genomes AF: 0.0804 AC: 12225 AN: 152024 Hom.: 690 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0632

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0684

GnomAD3 exomes AF: 0.0814 AC: 19968 AN: 245250 Hom.: 1173 AF XY: 0.0809 AC XY: 10810 AN XY: 133654

Gnomad AFR exome AF: 0.0205

Gnomad AMR exome AF: 0.0408

Gnomad ASJ exome AF: 0.0604

Gnomad EAS exome AF: 0.0130

Gnomad SAS exome AF: 0.0277

Gnomad FIN exome AF: 0.198

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.0830

GnomAD4 exome AF: 0.101 AC: 147128 AN: 1460098 Hom.: 8423 Cov.: 37 AF XY: 0.0986 AC XY: 71643 AN XY: 726290

Gnomad4 AFR exome AF: 0.0193

Gnomad4 AMR exome AF: 0.0424

Gnomad4 ASJ exome AF: 0.0597

Gnomad4 EAS exome AF: 0.0352

Gnomad4 SAS exome AF: 0.0293

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.0838

GnomAD4 genome AF: 0.0804 AC: 12229 AN: 152142 Hom.: 691 Cov.: 32 AF XY: 0.0839 AC XY: 6242 AN XY: 74368

Gnomad4 AFR AF: 0.0225

Gnomad4 AMR AF: 0.0630

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0968 Hom.: 769

Bravo AF: 0.0669

Asia WGS AF: 0.0220 AC: 76 AN: 3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.1
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1042116; hg19: chr6-32798548; COSMIC: COSV66501383; COSMIC: COSV66501383;