rs3819721

Variant names:

• chr6-32837021-G-A
• rs3819721
• NM_001290043.2:c.608+516C>T

Variant summary

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

The NM_001290043.2(TAP2):​c.608+516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,094 control chromosomes in the GnomAD database, including 5,230 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5230 hom., cov: 32)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 48 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000250264 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_001290043.2	c.608+516C>T		intron_variant	Intron 3 of 11	ENST00000374897.4	NP_001276972.1
TAP2	NM_018833.3	c.608+516C>T		intron_variant	Intron 3 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAP2	ENST00000374897.4	c.608+516C>T		intron_variant	Intron 3 of 11	1	NM_001290043.2	ENSP00000364032.3
ENSG00000250264	ENST00000452392.2	c.608+516C>T		intron_variant	Intron 3 of 14	2		ENSP00000391806.2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39324 AN: 151978 Hom.: 5202 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.218

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39411 AN: 152094 Hom.: 5230 Cov.: 32 AF XY: 0.262 AC XY: 19486 AN XY: 74334

African (AFR) AF: 0.296 AC: 12290 AN: 41458

American (AMR) AF: 0.185 AC: 2825 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3464

East Asian (EAS) AF: 0.310 AC: 1606 AN: 5186

South Asian (SAS) AF: 0.313 AC: 1512 AN: 4826

European-Finnish (FIN) AF: 0.294 AC: 3108 AN: 10562

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16538 AN: 67992

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.249 Hom.: 20031

Bravo AF: 0.252

Asia WGS AF: 0.299 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.89
PhyloP100		-0.21
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: rs3819721; hg19: chr6-32804798;