rs241424

Variant names:

• chr6-32837157-G-A
• rs241424
• NM_001290043.2:c.608+380C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32837157-G-A
• chr6-32837157-G-C
• chr6-32837157-G-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+380C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 151,912 control chromosomes in the GnomAD database, including 19,783 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 0.50 (19783 hom., cov: 31)
• Consequence: TAP2 NM_001290043.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 37 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	NM_001290043.2	MANE Select	c.608+380C>T		intron	N/A	NP_001276972.1
	TAP2	NM_018833.3		c.608+380C>T		intron	N/A	NP_061313.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAP2	ENST00000374897.4	TSL:1 MANE Select	c.608+380C>T		intron	N/A	ENSP00000364032.3
	ENSG00000250264	ENST00000452392.2	TSL:2	c.608+380C>T		intron	N/A	ENSP00000391806.2
	TAP2	ENST00000698449.1		c.608+380C>T		intron	N/A	ENSP00000513734.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76426 AN: 151794 Hom.: 19774 Cov.: 31

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.503 AC: 76467 AN: 151912 Hom.: 19783 Cov.: 31 AF XY: 0.500 AC XY: 37115 AN XY: 74222

African (AFR) AF: 0.602 AC: 24933 AN: 41400

American (AMR) AF: 0.544 AC: 8300 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1685 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2571 AN: 5164

South Asian (SAS) AF: 0.487 AC: 2341 AN: 4808

European-Finnish (FIN) AF: 0.414 AC: 4356 AN: 10532

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30613 AN: 67954

Other (OTH) AF: 0.509 AC: 1073 AN: 2110

Alfa AF: 0.476 Hom.: 73732

Bravo AF: 0.521

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.36
DANN	Benign	0.25
PhyloP100		-1.1
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: rs241424; hg19: chr6-32804934;