13-93830263-CACAGAGCTGAAAAGGTACT-C

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

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 9.60
Variant links:
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]

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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 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
GPC6NM_005708.5 linkuse as main transcriptc.433_451delGAGCTGAAAAGGTACTACA p.Glu145fs frameshift_variant 3/9 ENST00000377047.9 NP_005699.1 Q9Y625
GPC6XM_017020300.2 linkuse as main transcriptc.223_241delGAGCTGAAAAGGTACTACA p.Glu75fs frameshift_variant 3/9 XP_016875789.1
GPC6XM_047429990.1 linkuse as main transcriptc.223_241delGAGCTGAAAAGGTACTACA p.Glu75fs frameshift_variant 3/9 XP_047285946.1
GPC6-AS2NR_046536.1 linkuse as main transcriptn.380+534_380+552delAGTACCTTTTCAGCTCTGT intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPC6ENST00000377047.9 linkuse as main transcriptc.433_451delGAGCTGAAAAGGTACTACA p.Glu145fs frameshift_variant 3/91 NM_005708.5 ENSP00000366246.3 Q9Y625
GPC6-AS2ENST00000445540.1 linkuse as main transcriptn.228+534_228+552delAGTACCTTTTCAGCTCTGT intron_variant 5

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 31, 2020This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-94482516; API