Submissions for variant NM_020751.3(COG6):c.1167-24A>G

dbSNP: rs730882236

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000322754	SCV000332955	likely pathogenic	not provided	2015-07-09	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV001251035	SCV001426429	pathogenic	COG6-congenital disorder of glycosylation		criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001251035	SCV001524651	pathogenic	COG6-congenital disorder of glycosylation	2020-06-03	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV000322754	SCV001828048	pathogenic	not provided	2022-05-08	criteria provided, single submitter	clinical testing	RT-PCR analysis shows a significant reduction of the normal transcript and the presence of an aberrant COG6 transcript (Shaheen et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 25558065, 23606727, 26260076, 26077850, 29709711, 28600779, 28742265, 31589614, 29878199, 31130284, 32552793, 32860008)
Revvity Omics, Revvity	RCV000322754	SCV003821283	pathogenic	not provided	2022-05-18	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001251035	SCV004805072	pathogenic	COG6-congenital disorder of glycosylation	2024-03-17	criteria provided, single submitter	research
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000050228	SCV005420403	pathogenic	Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome	2024-10-04	criteria provided, single submitter	research	PM3 (very strong), PS3,PM2,PP1
OMIM	RCV000050228	SCV000082807	pathogenic	Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome	2013-07-01	no assertion criteria provided	literature only
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000162165	SCV000196451	likely pathogenic	Hypohidrosis; Intellectual disability	2014-12-01	no assertion criteria provided	research
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000985030	SCV001132963	pathogenic	COG6-related disorder	2019-08-25	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000985030	SCV004710980	pathogenic	COG6-related disorder	2024-02-14	no assertion criteria provided	clinical testing	The COG6 c.1167-24A>G variant is predicted to interfere with splicing. This variant was reported in the homozygous state in individuals with COG6-congenital disorder of glycosylation including hypohidrosis and intellectual disability features (Shaheen et al. 2013. PubMed ID: 23606727; Alsubhi et al. 2017. PubMed ID: 28742265; Monies et al. 2017. PubMed ID: 28600779; Monies et al. 2019. PubMed ID: 31130284; Maddirevula et al. 2020. PubMed ID: 32552793; Bertoli-Avella et al. 2021. PubMed ID: 32860008). This variant was reported as one of the founder variants for congenital disorders of glycosylation in Saudi population (Shaheen et al. 2013. PubMed ID: 23606727; Alsubhi et al. 2017. PubMed ID: 28742265). Functional studies showed this variant largely replaces the canonical acceptor site, resulting in pronounced reduction of the normal transcript and consequent deficiency of COG6 protein (Shaheen et al. 2013. PubMed ID: 23606727). This variant has not been reported in a large population database. This variant is interpreted as pathogenic.