chr2-203868009-ACT-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005214.5(CTLA4):c.71_72del(p.Leu24ProfsTer35) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
CTLA4
NM_005214.5 frameshift
NM_005214.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.119
Genes affected
CTLA4 (HGNC:2505): (cytotoxic T-lymphocyte associated protein 4) This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 30 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-203868009-ACT-A is Pathogenic according to our data. Variant chr2-203868009-ACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 1439020.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTLA4 | NM_005214.5 | c.71_72del | p.Leu24ProfsTer35 | frameshift_variant | 1/4 | ENST00000648405.2 | |
CTLA4 | NM_001037631.3 | c.71_72del | p.Leu24ProfsTer35 | frameshift_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTLA4 | ENST00000648405.2 | c.71_72del | p.Leu24ProfsTer35 | frameshift_variant | 1/4 | NM_005214.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with CTLA4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu24Profs*35) in the CTLA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTLA4 are known to be pathogenic (PMID: 25213377, 25329329). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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
Publications
No publications associated with this variant yet.