Genetic Variant ENSG00000250264:c.1933-5438G>A (chr6-32822390-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000452392.2(ENSG00000250264):c.1933-5438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENSG00000250264
ENST00000452392.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.780

Publications

11 publications found

Variant links:

Genes affected

ENSG00000250264 (HGNC:):

ENSG00000250264 links:

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

TAP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAP2	NM_018833.3 link	c.1933-72G>A		intron_variant	Intron 11 of 11		NP_061313.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ENSG00000250264	ENST00000452392.2 link	c.1933-5438G>A	intron_variant	Intron 11 of 14	2	ENSP00000391806.2
TAP2	ENST00000652259.1 link	c.1933-72G>A	intron_variant	Intron 11 of 11		ENSP00000498827.1
ENSG00000307274	ENST00000824890.1 link	n.79+1510C>T	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

854212

Hom.:

AF XY:

0.00

AC XY:

AN XY:

439950

African (AFR)

AF:

0.00

AC:

AN:

17956

American (AMR)

AF:

0.00

AC:

AN:

21448

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19818

East Asian (EAS)

AF:

0.00

AC:

AN:

32676

South Asian (SAS)

AF:

0.00

AC:

AN:

61250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3090

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

613158

Other (OTH)

AF:

0.00

AC:

AN:

39010

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.75

(source)

DANN

Benign

0.40

PhyloP100

-0.78

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over