GeneBe

ENST00000355480.10:c.67delG

Variant names:

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The ENST00000355480.10(COL18A1):​c.67delG​(p.Ala23ProfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

COL18A1
ENST00000355480.10 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92
Variant links:
Genes affected
COL18A1 (HGNC:2195): (collagen type XVIII alpha 1 chain) This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. A long isoform of the protein has an N-terminal domain that is homologous to the extracellular part of frizzled receptors. Proteolytic processing at several endogenous cleavage sites in the C-terminal domain results in production of endostatin, a potent antiangiogenic protein that is able to inhibit angiogenesis and tumor growth. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 91 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL18A1NM_001379500.1 linkc.107-12645delG intron_variant Intron 2 of 41 ENST00000651438.1 NP_001366429.1
COL18A1NM_130444.3 linkc.67delG p.Ala23ProfsTer4 frameshift_variant Exon 1 of 41 NP_569711.2 P39060
COL18A1NM_030582.4 linkc.67delG p.Ala23ProfsTer4 frameshift_variant Exon 1 of 41 NP_085059.2 P39060D3DSM5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL18A1ENST00000355480.10 linkc.67delG p.Ala23ProfsTer4 frameshift_variant Exon 1 of 41 1 ENSP00000347665.5 P39060-1
COL18A1ENST00000651438.1 linkc.107-12645delG intron_variant Intron 2 of 41 NM_001379500.1 ENSP00000498485.1 P39060-2
COL18A1ENST00000359759.8 linkc.67delG p.Ala23ProfsTer4 frameshift_variant Exon 1 of 41 5 ENSP00000352798.4 P39060-3

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461604
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: chr21-46875508; API