rs1555860555
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001379500.1(COL18A1):c.1070delC(p.Pro357GlnfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,278 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
COL18A1
NM_001379500.1 frameshift
NM_001379500.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.71
Publications
0 publications found
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]
COL18A1 Gene-Disease associations (from GenCC):
- Knobloch syndrome 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
- Knobloch syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet
- hereditary glaucoma, primary closed-angleInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 21-45477808-GC-G is Pathogenic according to our data. Variant chr21-45477808-GC-G is described in ClinVar as Pathogenic. ClinVar VariationId is 1442812.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001379500.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| COL18A1 | NM_001379500.1 | MANE Select | c.1070delC | p.Pro357GlnfsTer16 | frameshift | Exon 8 of 42 | NP_001366429.1 | P39060-2 | |
| COL18A1 | NM_130444.3 | c.2315delC | p.Pro772GlnfsTer16 | frameshift | Exon 7 of 41 | NP_569711.2 | |||
| COL18A1 | NM_030582.4 | c.1610delC | p.Pro537GlnfsTer16 | frameshift | Exon 7 of 41 | NP_085059.2 | A0AAG2UXZ5 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| COL18A1 | ENST00000651438.1 | MANE Select | c.1070delC | p.Pro357GlnfsTer16 | frameshift | Exon 8 of 42 | ENSP00000498485.1 | P39060-2 | |
| COL18A1 | ENST00000355480.10 | TSL:1 | c.1610delC | p.Pro537GlnfsTer16 | frameshift | Exon 7 of 41 | ENSP00000347665.5 | P39060-1 | |
| COL18A1 | ENST00000359759.8 | TSL:5 | c.2315delC | p.Pro772GlnfsTer16 | frameshift | Exon 7 of 41 | ENSP00000352798.4 | P39060-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1398278Hom.: 0 Cov.: 33 AF XY: 0.00000145 AC XY: 1AN XY: 689744 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1398278
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
689744
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31708
American (AMR)
AF:
AC:
0
AN:
35770
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25130
East Asian (EAS)
AF:
AC:
0
AN:
35922
South Asian (SAS)
AF:
AC:
1
AN:
79278
European-Finnish (FIN)
AF:
AC:
0
AN:
47758
Middle Eastern (MID)
AF:
AC:
0
AN:
5676
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1079052
Other (OTH)
AF:
AC:
0
AN:
57984
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
not provided (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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