13-93830263-CACAGAGCTGAAAAGGTACT-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_005708.5(GPC6):c.433_451delGAGCTGAAAAGGTACTACA(p.Glu145fs) variant causes a frameshift change involving the alteration of a 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: 31)
Consequence
GPC6
NM_005708.5 frameshift
NM_005708.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.60
Genes affected
GPC6 (HGNC:4454): (glypican 6) The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]
Genome browser will be placed here
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 13-93830263-CACAGAGCTGAAAAGGTACT-C is Pathogenic according to our data. Variant chr13-93830263-CACAGAGCTGAAAAGGTACT-C is described in ClinVar as [Pathogenic]. Clinvar id is 1076013.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPC6 | NM_005708.5 | c.433_451delGAGCTGAAAAGGTACTACA | p.Glu145fs | frameshift_variant | 3/9 | ENST00000377047.9 | NP_005699.1 | |
GPC6 | XM_017020300.2 | c.223_241delGAGCTGAAAAGGTACTACA | p.Glu75fs | frameshift_variant | 3/9 | XP_016875789.1 | ||
GPC6 | XM_047429990.1 | c.223_241delGAGCTGAAAAGGTACTACA | p.Glu75fs | frameshift_variant | 3/9 | XP_047285946.1 | ||
GPC6-AS2 | NR_046536.1 | n.380+534_380+552delAGTACCTTTTCAGCTCTGT | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GPC6 | ENST00000377047.9 | c.433_451delGAGCTGAAAAGGTACTACA | p.Glu145fs | frameshift_variant | 3/9 | 1 | NM_005708.5 | ENSP00000366246.3 | ||
GPC6-AS2 | ENST00000445540.1 | n.228+534_228+552delAGTACCTTTTCAGCTCTGT | intron_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
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 | Labcorp Genetics (formerly Invitae), Labcorp | Aug 31, 2020 | This sequence change creates a premature translational stop signal (p.Glu145Leufs*5) in the GPC6 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GPC6-related conditions. Loss-of-function variants in GPC6 are known to be pathogenic (PMID: 19481194). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.