chr15-51342013-AC-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_181789.4(GLDN):c.330del(p.Asp110GlufsTer3) 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
GLDN
NM_181789.4 frameshift
NM_181789.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.00
Genes affected
GLDN (HGNC:29514): (gliomedin) This gene encodes a protein that contains olfactomedin-like and collagen-like domains. The encoded protein, which exists in both transmembrane and secreted forms, promotes formation of the nodes of Ranvier in the peripheral nervous system. Mutations in this gene cause a form of lethal congenital contracture syndrome in human patients. Autoantibodies to the encoded protein have been identified in sera form patients with multifocal motor neuropathy. [provided by RefSeq, May 2017]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-51342013-AC-A is Pathogenic according to our data. Variant chr15-51342013-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 523974.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLDN | NM_181789.4 | c.330del | p.Asp110GlufsTer3 | frameshift_variant | 1/10 | ENST00000335449.11 | |
GLDN | XM_017022121.2 | c.330del | p.Asp110GlufsTer3 | frameshift_variant | 1/9 | ||
GLDN | XM_017022125.1 | c.330del | p.Asp110GlufsTer3 | frameshift_variant | 1/10 | ||
GLDN | XM_017022126.3 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLDN | ENST00000335449.11 | c.330del | p.Asp110GlufsTer3 | frameshift_variant | 1/10 | 2 | NM_181789.4 | P1 | |
GLDN | ENST00000558286.5 | n.141del | non_coding_transcript_exon_variant | 1/3 | 1 | ||||
GLDN | ENST00000560690.5 | n.69del | non_coding_transcript_exon_variant | 1/4 | 1 | ||||
GLDN | ENST00000560215.5 | c.217del | p.Asp73GlufsTer3 | frameshift_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
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
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 21, 2020 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
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Prediction
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