12-8605439-C-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_020661.4(AICDA):c.203G>A(p.Trp68*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_020661.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AICDA | NM_020661.4 | c.203G>A | p.Trp68* | stop_gained | Exon 3 of 5 | ENST00000229335.11 | NP_065712.1 | |
AICDA | NM_001330343.2 | c.203G>A | p.Trp68* | stop_gained | Exon 3 of 5 | NP_001317272.1 | ||
AICDA | NM_001410970.1 | c.203G>A | p.Trp68* | stop_gained | Exon 3 of 4 | NP_001397899.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hyper-IgM syndrome type 2 Pathogenic:2
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For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 5123). This premature translational stop signal has been observed in individual(s) with autosomal recessive hyper IgM syndrome (PMID: 11007475, 14962793). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp68*) in the AICDA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AICDA are known to be pathogenic (PMID: 11007475). -
not provided Pathogenic:1
AICDA: PVS1, PM2 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at