rs1555763342
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_002361.4(MAG):c.416-6_418dup variant causes a splice region, splice polypyrimidine tract, intron 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 28)
Consequence
MAG
NM_002361.4 splice_region, splice_polypyrimidine_tract, intron
NM_002361.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -3.34
Genes affected
MAG (HGNC:6783): (myelin associated glycoprotein) The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-35299547-C-CGTATAGACA is Pathogenic according to our data. Variant chr19-35299547-C-CGTATAGACA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 435794.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAG | NM_002361.4 | c.416-6_418dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000392213.8 | |||
MAG | NM_001199216.2 | c.341-6_343dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
MAG | NM_080600.3 | c.416-6_418dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAG | ENST00000392213.8 | c.416-6_418dup | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_002361.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 28
GnomAD3 genomes
?
Cov.:
28
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 28
GnomAD4 genome
?
Cov.:
28
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 22, 2021 | DNA sequence analysis of the MAG gene demonstrated a 9 base pair duplication involving nucleotides in intron 5 and exon 6, c.416-6_418dup. This sequence change is absent from known population databases (gnomAD). The impact of this variant on splicing is unclear, however it is possible this duplication results in an in-frame insertion of three amino acid residues. This sequence change does not appear to have been previously described in patients with MAG-related disorders and has also not been described as a known benign sequence change in the MAG gene. Targeted sequence analysis of the MAG variant in this family indicated that this homozygous variant co-segregated with disease in this individual’s affected mother, sister, and brother. Taken together, this variant has been re-classified as likely pathogenic. Functional studies have not been performed to prove this conclusively. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at