rs1085307116
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_007357.3(COG2):c.701dup(p.Tyr234Ter) variant causes a stop gained, frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
COG2
NM_007357.3 stop_gained, frameshift
NM_007357.3 stop_gained, frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.06
Genes affected
COG2 (HGNC:6546): (component of oligomeric golgi complex 2) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi complex. The encoded protein specifically interacts with the USO1 vesicle docking protein and may be necessary for normal Golgi ribbon formation and trafficking of Golgi enzymes. Mutations of this gene are associated with abnormal glycosylation within the Golgi apparatus. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 1-230669461-T-TA is Pathogenic according to our data. Variant chr1-230669461-T-TA is described in ClinVar as [Pathogenic]. Clinvar id is 417770.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG2 | NM_007357.3 | c.701dup | p.Tyr234Ter | stop_gained, frameshift_variant | 7/18 | ENST00000366669.9 | |
COG2 | NM_001145036.2 | c.701dup | p.Tyr234Ter | stop_gained, frameshift_variant | 7/18 | ||
COG2 | XM_047449445.1 | c.362dup | p.Tyr121Ter | stop_gained, frameshift_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG2 | ENST00000366669.9 | c.701dup | p.Tyr234Ter | stop_gained, frameshift_variant | 7/18 | 1 | NM_007357.3 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461792Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727192
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31
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727192
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital disorder of glycosylation, type IIq Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 26, 2017 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at