ClinVar Miner

Submissions for variant NM_006348.5(COG5):c.1776T>C (p.Ala592=)

gnomAD frequency: 0.00142  dbSNP: rs142970891
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000364992 SCV000466033 uncertain significance COG5-congenital disorder of glycosylation 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000431642 SCV000521823 likely benign not specified 2017-11-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000364992 SCV002369084 benign COG5-congenital disorder of glycosylation 2024-01-27 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV000364992 SCV001445935 likely benign COG5-congenital disorder of glycosylation 2020-11-16 no assertion criteria provided curation The heterozygous c.1869T>C variant in COG5 was identified by our study in the compound heterozygous state, along with a variant of unknown significance, in 1 individual with congenital disorder of glycosylation, type IIi (commonly referred to as COG5-CDG or CDG2I). The variant has not been previously reported in individuals with COG5-CDG and has been identified in 0.29% (30/10352) of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs142970891). This variant has also been reported in ClinVar (Variation ID#: 358457) as likely benign by GeneDx and as uncertain significance by Illumina Clinical Services Laboratory. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BS1, BP4, BP7 (Richards 2015).

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