rs241448

Positions:

• chr6-32828908-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BA1

The NM_001290043.2(TAP2):​c.2059T>C​(p.Ter687GlnextTer17) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,543,082 control chromosomes in the GnomAD database, including 58,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5925 hom., cov: 30)
  • Exomes 𝑓: 0.27 (52954 hom.)
• Consequence: TAP2 NM_001290043.2 stop_lost
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.36

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 -14 ACMG points.

• PM4: Stoplost variant in NM_001290043.2 Downstream stopcodon found after 42 codons.
• BP6: Variant 6-32828908-A-G is Benign according to our data. Variant chr6-32828908-A-G is described in ClinVar as [Benign]. Clinvar id is 403510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32828908-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.2059T>C	p.Ter687GlnextTer17	stop_lost	12/12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1932+492T>C		intron_variant			NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.2059T>C	p.Ter687GlnextTer17	stop_lost	12/12	1	NM_001290043.2	ENSP00000364032	A2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41592 AN: 151740 Hom.: 5915 Cov.: 30

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.296

GnomAD3 exomes AF: 0.316 AC: 47140 AN: 148998 Hom.: 7808 AF XY: 0.318 AC XY: 25415 AN XY: 80040

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.356

Gnomad ASJ exome AF: 0.343

Gnomad EAS exome AF: 0.361

Gnomad SAS exome AF: 0.394

Gnomad FIN exome AF: 0.343

Gnomad NFE exome AF: 0.262

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.270 AC: 376064 AN: 1391224 Hom.: 52954 Cov.: 39 AF XY: 0.274 AC XY: 187494 AN XY: 685394

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.349

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.274 AC: 41625 AN: 151858 Hom.: 5925 Cov.: 30 AF XY: 0.282 AC XY: 20934 AN XY: 74220

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.296

Alfa AF: 0.273 Hom.: 8801

Bravo AF: 0.270

TwinsUK AF: 0.225 AC: 833

ALSPAC AF: 0.238 AC: 919

ESP6500AA AF: 0.161 AC: 385

ESP6500EA AF: 0.190 AC: 895

ExAC AF: 0.145 AC: 11752

Asia WGS AF: 0.366 AC: 1274 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

MHC class I deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.019
DANN	Benign	0.32
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
GERP RS		-12

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: rs241448; hg19: chr6-32796685; COSMIC: COSV66498061; COSMIC: COSV66498061;