Submissions for variant NM_000393.5(COL5A2):c.2895A>G (p.Pro965=)

gnomAD frequency: 0.00008  dbSNP: rs760946138

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001712190	SCV000512722	likely benign	not provided	2019-07-19	criteria provided, single submitter	clinical testing
Invitae	RCV002229997	SCV000558986	likely benign	Ehlers-Danlos syndrome, classic type, 1	2024-01-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001143724	SCV001304273	likely benign	Ehlers-Danlos syndrome, classic type, 2	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278656	SCV002565824	likely benign	Ehlers-Danlos syndrome	2020-04-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436245	SCV002750570	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2022-06-06	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.
Fulgent Genetics, Fulgent Genetics	RCV001143724	SCV002807476	likely benign	Ehlers-Danlos syndrome, classic type, 2	2021-08-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003972572	SCV004795004	likely benign	COL5A2-related condition	2022-08-24	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).