rs241441

Positions:

• chr6-32829520-T-C

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.1812A>G​(p.Gly604=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,613,800 control chromosomes in the GnomAD database, including 61,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5582 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55787 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.69

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=-0.83).
• BP6: Variant 6-32829520-T-C is Benign according to our data. Variant chr6-32829520-T-C is described in ClinVar as [Benign]. Clinvar id is 403513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32829520-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-3.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.1812A>G	p.Gly604=	synonymous_variant	11/12	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.1812A>G	p.Gly604=	synonymous_variant	11/12		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.1812A>G	p.Gly604=	synonymous_variant	11/12	1	NM_001290043.2	ENSP00000364032	A2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39965 AN: 152036 Hom.: 5573 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.286

GnomAD3 exomes AF: 0.303 AC: 76069 AN: 251004 Hom.: 12106 AF XY: 0.306 AC XY: 41539 AN XY: 135650

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.360

Gnomad SAS exome AF: 0.399

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.270 AC: 395196 AN: 1461646 Hom.: 55787 Cov.: 53 AF XY: 0.274 AC XY: 199227 AN XY: 727092

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.263 AC: 39995 AN: 152154 Hom.: 5582 Cov.: 32 AF XY: 0.271 AC XY: 20149 AN XY: 74398

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.287

Alfa AF: 0.268 Hom.: 10681

Bravo AF: 0.256

Asia WGS AF: 0.362 AC: 1258 AN: 3478

EpiCase AF: 0.266

EpiControl AF: 0.269

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.65

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: rs241441; hg19: chr6-32797297; COSMIC: COSV66500323; COSMIC: COSV66500323;