rs886041056
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_181789.4(GLDN):c.758delC(p.Pro253LeufsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,447,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
GLDN
NM_181789.4 frameshift
NM_181789.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.81
Publications
0 publications found
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]
GLDN Gene-Disease associations (from GenCC):
- lethal congenital contracture syndrome 11Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 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 15-51397534-GC-G is Pathogenic according to our data. Variant chr15-51397534-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 268104.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_181789.4. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GLDN | TSL:2 MANE Select | c.758delC | p.Pro253LeufsTer51 | frameshift | Exon 6 of 10 | ENSP00000335196.6 | Q6ZMI3-1 | ||
| GLDN | TSL:1 | c.386delC | p.Pro129LeufsTer51 | frameshift | Exon 6 of 10 | ENSP00000379681.2 | Q6ZMI3-2 | ||
| GLDN | c.740delC | p.Pro247LeufsTer51 | frameshift | Exon 5 of 9 | ENSP00000527882.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1447418Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 719954 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1447418
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
719954
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
33000
American (AMR)
AF:
AC:
0
AN:
43768
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25838
East Asian (EAS)
AF:
AC:
0
AN:
38226
South Asian (SAS)
AF:
AC:
0
AN:
84054
European-Finnish (FIN)
AF:
AC:
0
AN:
53056
Middle Eastern (MID)
AF:
AC:
0
AN:
5710
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1104106
Other (OTH)
AF:
AC:
0
AN:
59660
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
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2
3
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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10
<30
30-35
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Lethal congenital contracture syndrome 11 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
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