chr21-45486944-CCCCCCTGGGCCCCCTGGG-C

Variant names:

• chr21-45486944-CCCCCCTGGGCCCCCTGGG-C
• NM_001379500.1:c.1791_1808delTGGGCCCCCTGGGCCCCC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001379500.1(COL18A1):​c.1791_1808delTGGGCCCCCTGGGCCCCC​(p.Gly598_Pro603del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000749 in 1,334,512 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: 33)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: COL18A1 NM_001379500.1 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001379500.1.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.1791_1808delTGGGCCCCCTGGGCCCCC	p.Gly598_Pro603del	disruptive_inframe_deletion	Exon 16 of 42	ENST00000651438.1	NP_001366429.1
COL18A1	NM_130444.3	c.3036_3053delTGGGCCCCCTGGGCCCCC	p.Gly1013_Pro1018del	disruptive_inframe_deletion	Exon 15 of 41		NP_569711.2
COL18A1	NM_030582.4	c.2331_2348delTGGGCCCCCTGGGCCCCC	p.Gly778_Pro783del	disruptive_inframe_deletion	Exon 15 of 41		NP_085059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.1791_1808delTGGGCCCCCTGGGCCCCC	p.Gly598_Pro603del	disruptive_inframe_deletion	Exon 16 of 42		NM_001379500.1	ENSP00000498485.1
COL18A1	ENST00000355480.10	c.2331_2348delTGGGCCCCCTGGGCCCCC	p.Gly778_Pro783del	disruptive_inframe_deletion	Exon 15 of 41	1		ENSP00000347665.5
COL18A1	ENST00000359759.8	c.3036_3053delTGGGCCCCCTGGGCCCCC	p.Gly1013_Pro1018del	disruptive_inframe_deletion	Exon 15 of 41	5		ENSP00000352798.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.49e-7 AC: 1 AN: 1334512 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 656314

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000289

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.: 33

ClinVar

Not reported in ClinVar

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: chr21-46906858;