Submissions for variant NM_000393.5(COL5A2):c.4450G>A (p.Gly1484Ser)

gnomAD frequency: 0.00041  dbSNP: rs147420365

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000195469	SCV000249947	uncertain significance	not provided	2018-11-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the COL5A2 gene. The G1484S variant has not been published as pathogenic or been reported as benign to our knowledge, yet this variant has been identified independently and/or in conjunction with additional variants in other unrelated individuals referred for genetic testing at GeneDx. So far, segregation data is limited or absent for these individuals. The G1484S variant is observed in 80/126,512 (0.06%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). Finally, though G1484S is a non-conservative amino acid substitution, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Invitae	RCV002229083	SCV000547865	likely benign	Ehlers-Danlos syndrome, classic type, 1	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315567	SCV000738691	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2017-04-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000195469	SCV001153236	likely benign	not provided	2021-10-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001801464	SCV002048389	likely benign	Ehlers-Danlos syndrome, classic type, 2	2021-07-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003323442	SCV004028674	likely benign	not specified	2023-07-21	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927819	SCV004746705	likely benign	COL5A2-related condition	2022-04-15	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000195469	SCV001807615	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000195469	SCV001932004	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000195469	SCV001973062	likely benign	not provided		no assertion criteria provided	clinical testing