6-32830506-T-C

Variant names:

• chr6-32830506-T-C
• rs9380326
• NM_001290043.2:c.1462-66A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001290043.2(TAP2):​c.1462-66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,591,314 control chromosomes in the GnomAD database, including 12,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1089 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11139 hom.)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 25 publications found

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]

TAP2 Gene-Disease associations (from GenCC):

• MHC class I deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
• MHC class I deficiency 1

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

ENSG00000250264 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290043.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.1462-66A>G		intron	N/A	NP_001276972.1	Q5JNW1
	TAP2	NM_018833.3		c.1462-66A>G		intron	N/A	NP_061313.2	Q9UP03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.1462-66A>G		intron	N/A	ENSP00000364032.3	Q03519-1
	ENSG00000250264	ENST00000452392.2	TSL:2	c.1462-66A>G		intron	N/A	ENSP00000391806.2	E7ENX8
	TAP2	ENST00000698449.1		c.1495-66A>G		intron	N/A	ENSP00000513734.1	A0A8V8TNJ0

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16856 AN: 152124 Hom.: 1088 Cov.: 32

Gnomad AFR AF: 0.0664

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.0811

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.121 AC: 174183 AN: 1439072 Hom.: 11139 Cov.: 37 AF XY: 0.120 AC XY: 85591 AN XY: 714276

African (AFR) AF: 0.0627 AC: 2049 AN: 32696

American (AMR) AF: 0.0967 AC: 3934 AN: 40674

Ashkenazi Jewish (ASJ) AF: 0.0770 AC: 1977 AN: 25674

East Asian (EAS) AF: 0.0912 AC: 3497 AN: 38348

South Asian (SAS) AF: 0.0826 AC: 6937 AN: 83968

European-Finnish (FIN) AF: 0.218 AC: 11192 AN: 51286

Middle Eastern (MID) AF: 0.0635 AC: 354 AN: 5576

European-Non Finnish (NFE) AF: 0.125 AC: 137891 AN: 1101176

Other (OTH) AF: 0.106 AC: 6352 AN: 59674

GnomAD4 genome AF: 0.111 AC: 16867 AN: 152242 Hom.: 1089 Cov.: 32 AF XY: 0.116 AC XY: 8618 AN XY: 74438

African (AFR) AF: 0.0665 AC: 2764 AN: 41570

American (AMR) AF: 0.109 AC: 1660 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.0920 AC: 476 AN: 5174

South Asian (SAS) AF: 0.0813 AC: 392 AN: 4820

European-Finnish (FIN) AF: 0.229 AC: 2420 AN: 10590

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8443 AN: 68004

Other (OTH) AF: 0.106 AC: 223 AN: 2110

Alfa AF: 0.112 Hom.: 2752

Bravo AF: 0.0993

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.44
PhyloP100		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9380326; hg19: chr6-32798283;