13-93830263-CACAGAGCTGAAAAGGTACT-C

Variant names:

• chr13-93830263-CACAGAGCTGAAAAGGTACT-C
• NM_005708.5:c.433_451delGAGCTGAAAAGGTACTACA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_005708.5(GPC6):​c.433_451delGAGCTGAAAAGGTACTACA​(p.Glu145LeufsTer5) 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
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• 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]

GPC6-AS2 (HGNC:39910): (GPC6 antisense RNA 2)

ACMG classification

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 rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.433_451delGAGCTGAAAAGGTACTACA	p.Glu145LeufsTer5	frameshift_variant	Exon 3 of 9	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.223_241delGAGCTGAAAAGGTACTACA	p.Glu75LeufsTer5	frameshift_variant	Exon 3 of 9		XP_016875789.1
GPC6	XM_047429990.1	c.223_241delGAGCTGAAAAGGTACTACA	p.Glu75LeufsTer5	frameshift_variant	Exon 3 of 9		XP_047285946.1
GPC6-AS2	NR_046536.1	n.380+534_380+552delAGTACCTTTTCAGCTCTGT		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.433_451delGAGCTGAAAAGGTACTACA	p.Glu145LeufsTer5	frameshift_variant	Exon 3 of 9	1	NM_005708.5	ENSP00000366246.3
GPC6-AS2	ENST00000445540.1	n.228+534_228+552delAGTACCTTTTCAGCTCTGT		intron_variant	Intron 2 of 2	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

Submissions by phenotype

not provided Pathogenic:1

Aug 31, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GPC6 are known to be pathogenic (PMID: 19481194). This variant has not been reported in the literature in individuals with GPC6-related conditions. 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. -

Computational scores

Source: dbNSFP v4.3

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;