rs2856992
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001290043.2(TAP2):c.1161G>A(p.Val387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,612,722 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.020 ( 46 hom., cov: 32)
Exomes 𝑓: 0.024 ( 524 hom. )
Consequence
TAP2
NM_001290043.2 synonymous
NM_001290043.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.65
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 6-32832444-C-T is Benign according to our data. Variant chr6-32832444-C-T is described in ClinVar as [Benign]. Clinvar id is 466365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.65 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0204 (3105/152320) while in subpopulation AMR AF= 0.0283 (433/15302). AF 95% confidence interval is 0.0261. There are 46 homozygotes in gnomad4. There are 1378 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 46 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAP2 | NM_001290043.2 | c.1161G>A | p.Val387= | synonymous_variant | 7/12 | ENST00000374897.4 | |
TAP2 | NM_018833.3 | c.1161G>A | p.Val387= | synonymous_variant | 7/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAP2 | ENST00000374897.4 | c.1161G>A | p.Val387= | synonymous_variant | 7/12 | 1 | NM_001290043.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0204 AC: 3104AN: 152202Hom.: 46 Cov.: 32
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GnomAD3 exomes AF: 0.0145 AC: 3561AN: 245660Hom.: 45 AF XY: 0.0139 AC XY: 1863AN XY: 133854
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GnomAD4 exome AF: 0.0242 AC: 35398AN: 1460402Hom.: 524 Cov.: 32 AF XY: 0.0230 AC XY: 16727AN XY: 726462
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GnomAD4 genome ? AF: 0.0204 AC: 3105AN: 152320Hom.: 46 Cov.: 32 AF XY: 0.0185 AC XY: 1378AN XY: 74494
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MHC class I deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
TAP2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 09, 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
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at