rs145894663

chr6-32829412-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2 BP4_Strong BP6_Moderate BP7 BS1

The NM_001290043.2(TAP2):c.1920G>A(p.Gln640=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000671 in 1,604,242 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (1 hom.)
• Consequence: TAP2 NM_001290043.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0430

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 -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-32829412-C-T is Benign according to our data. Variant chr6-32829412-C-T is described in ClinVar as [Benign]. Clinvar id is 534715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.043 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000505 (77/152344) while in subpopulation AMR AF= 0.00222 (34/15312). AF 95% confidence interval is 0.00163. There are 0 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAP2	NM_001290043.2	c.1920G>A	p.Gln640=	synonymous_variant	11/12	ENST00000374897.4
TAP2	NM_018833.3	c.1920G>A	p.Gln640=	synonymous_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAP2	ENST00000374897.4	c.1920G>A	p.Gln640=	synonymous_variant	11/12	1	NM_001290043.2	A2

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000623 AC: 146 AN: 234268 Hom.: 0 AF XY: 0.000666 AC XY: 84 AN XY: 126176

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000496

Gnomad NFE exome AF: 0.000637

Gnomad OTH exome AF: 0.000856

GnomAD4 exome AF: 0.000689 AC: 1000 AN: 1451898 Hom.: 1 Cov.: 54 AF XY: 0.000692 AC XY: 499 AN XY: 721146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00171

Gnomad4 ASJ exome AF: 0.00190

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000171

Gnomad4 NFE exome AF: 0.000722

Gnomad4 OTH exome AF: 0.00115

GnomAD4 genome AF: 0.000505 AC: 77 AN: 152344 Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39 AN XY: 74492

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000637 Hom.: 0

Bravo AF: 0.000608

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class I deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	5.7
Dann	Benign	0.60

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: rs145894663; hg19: chr6-32797189; COSMIC: COSV100886976; COSMIC: COSV100886976;