10-13108910-G-GCGCGCACACA

Variant names:

• chr10-13108910-G-GCGCGCACACA
• NM_001008212.2:c.-11-201_-11-200insGCGCACACAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001008212.2(OPTN):​c.-11-201_-11-200insGCGCACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 438,488 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: 11)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777

Genes affected

OPTN (HGNC:17142): (optineurin) This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.-11-201_-11-200insGCGCACACAC		intron_variant	Intron 2 of 14	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.-80-51_-80-50insGCGCACACAC		intron_variant	Intron 2 of 15		NP_001008212.1
OPTN	NM_001008213.1	c.-65-51_-65-50insGCGCACACAC		intron_variant	Intron 2 of 15		NP_001008214.1
OPTN	NM_021980.4	c.-11-201_-11-200insGCGCACACAC		intron_variant	Intron 1 of 13		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.-11-202_-11-201insCGCGCACACA		intron_variant	Intron 2 of 14	1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome AF: 0.00000228 AC: 1 AN: 438488 Hom.: 0 AF XY: 0.00000427 AC XY: 1 AN XY: 234294

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: 0.00

Gnomad4 OTH exome AF: 0.0000409

GnomAD4 genome Cov.: 11

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: chr10-13150910;