21-45492744-G-GCCCGCCACGGCCCT

Variant names:

• chr21-45492744-G-GCCCGCCACGGCCCT
• NM_001379500.1:c.2214+35_2214+36insCCACGGCCCTCCCG

Variant summary

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

The NM_001379500.1(COL18A1):​c.2214+35_2214+36insCCACGGCCCTCCCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,386 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: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588

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 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.2214+35_2214+36insCCACGGCCCTCCCG		intron_variant	Intron 24 of 41	ENST00000651438.1	NP_001366429.1
COL18A1	NM_130444.3	c.3459+35_3459+36insCCACGGCCCTCCCG		intron_variant	Intron 23 of 40		NP_569711.2
COL18A1	NM_030582.4	c.2754+35_2754+36insCCACGGCCCTCCCG		intron_variant	Intron 23 of 40		NP_085059.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.2214+31_2214+32insCCCGCCACGGCCCT		intron_variant	Intron 24 of 41		NM_001379500.1	ENSP00000498485.1
COL18A1	ENST00000355480.10	c.2754+31_2754+32insCCCGCCACGGCCCT		intron_variant	Intron 23 of 40	1		ENSP00000347665.5
COL18A1	ENST00000359759.8	c.3459+31_3459+32insCCCGCCACGGCCCT		intron_variant	Intron 23 of 40	5		ENSP00000352798.4
COL18A1	ENST00000342220.9	c.255+31_255+32insCCCGCCACGGCCCT		intron_variant	Intron 5 of 22	2		ENSP00000339118.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151890 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000429 AC: 6 AN: 1399386 Hom.: 0 Cov.: 28 AF XY: 0.00000429 AC XY: 3 AN XY: 699234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000469

Gnomad4 OTH exome AF: 0.0000171

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151890 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 74168

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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: chr21-46912658;