rs1554464495
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_006348.5(COG5):βc.96delβ(p.Cys33ValfsTer6) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (β β ).
Frequency
Consequence
NM_006348.5 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COG5 | NM_006348.5 | c.96del | p.Cys33ValfsTer6 | frameshift_variant, splice_region_variant | 2/22 | ENST00000297135.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COG5 | ENST00000297135.9 | c.96del | p.Cys33ValfsTer6 | frameshift_variant, splice_region_variant | 2/22 | 1 | NM_006348.5 | P2 | |
COG5 | ENST00000347053.8 | c.96del | p.Cys33ValfsTer6 | frameshift_variant, splice_region_variant | 2/21 | 1 | A2 | ||
COG5 | ENST00000393603.7 | c.96del | p.Cys33ValfsTer6 | frameshift_variant, splice_region_variant | 2/21 | 1 | |||
COG5 | ENST00000605888.1 | c.96del | p.Cys33ValfsTer6 | frameshift_variant, splice_region_variant | 2/6 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461358Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726994
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
COG5-congenital disorder of glycosylation Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 09, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 29, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 523949). This premature translational stop signal has been observed in individual(s) with COG5-congenital disorder of glycosylation (PMID: 23228021). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys64Valfs*6) in the COG5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COG5 are known to be pathogenic (PMID: 23228021). - |
COG5-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 11, 2024 | The COG5 c.189delG variant is predicted to result in a frameshift and premature protein termination (p.Cys64Valfs*6). This variant has been reported in the compound heterozygous state in a patient with a congenital disorder of glycosylation (Patient 3, Rymen et al. 2012. PubMed ID: 2322802). To our knowledge, this variant has not been reported in the in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in COG5 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 28, 2019 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23228021) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at