rs111303994
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001290043.2(TAP2):c.1120G>A(p.Ala374Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00411 in 1,613,046 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 50 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 53 hom. )
Consequence
TAP2
NM_001290043.2 missense
NM_001290043.2 missense
Scores
8
9
Clinical Significance
Conservation
PhyloP100: 1.27
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0050628483).
BP6
Variant 6-32832650-C-T is Benign according to our data. Variant chr6-32832650-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 466362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2108/152260) while in subpopulation AFR AF= 0.0407 (1689/41534). AF 95% confidence interval is 0.0391. There are 50 homozygotes in gnomad4. There are 1034 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 50 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAP2 | NM_001290043.2 | c.1120G>A | p.Ala374Thr | missense_variant | 6/12 | ENST00000374897.4 | |
TAP2 | NM_018833.3 | c.1120G>A | p.Ala374Thr | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAP2 | ENST00000374897.4 | c.1120G>A | p.Ala374Thr | missense_variant | 6/12 | 1 | NM_001290043.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0138 AC: 2101AN: 152142Hom.: 50 Cov.: 32
GnomAD3 genomes
AF:
AC:
2101
AN:
152142
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00575 AC: 1419AN: 246652Hom.: 16 AF XY: 0.00436 AC XY: 586AN XY: 134430
GnomAD3 exomes
AF:
AC:
1419
AN:
246652
Hom.:
AF XY:
AC XY:
586
AN XY:
134430
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00310 AC: 4523AN: 1460786Hom.: 53 Cov.: 35 AF XY: 0.00285 AC XY: 2071AN XY: 726710
GnomAD4 exome
AF:
AC:
4523
AN:
1460786
Hom.:
Cov.:
35
AF XY:
AC XY:
2071
AN XY:
726710
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0138 AC: 2108AN: 152260Hom.: 50 Cov.: 32 AF XY: 0.0139 AC XY: 1034AN XY: 74448
GnomAD4 genome
AF:
AC:
2108
AN:
152260
Hom.:
Cov.:
32
AF XY:
AC XY:
1034
AN XY:
74448
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
3
ALSPAC
AF:
AC:
5
ESP6500AA
AF:
AC:
114
ESP6500EA
AF:
AC:
9
ExAC
AF:
AC:
725
Asia WGS
AF:
AC:
11
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MHC class I deficiency Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 13, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
TAP2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;.;.
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;M;.;M
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;.;D
REVEL
Uncertain
Sift
Benign
T;D;.;D
Sift4G
Benign
.;T;T;T
Polyphen
0.95
.;.;.;P
Vest4
0.20, 0.18, 0.19
MVP
MPC
0.68
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at