Submissions for variant NM_000093.5(COL5A1):c.2555A>G (p.Asn852Ser)

dbSNP: rs148146480

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000383952	SCV000478545	uncertain significance	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV002058782	SCV000631469	likely benign	Ehlers-Danlos syndrome, classic type, 1	2023-12-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000525069	SCV001328068	likely benign	Ehlers-Danlos syndrome, classic type	2018-01-12	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.
GeneDx	RCV001764335	SCV002009011	uncertain significance	not provided	2022-10-26	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (Symoens et al., 2012; HGMD)
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002058782	SCV002496070	uncertain significance	Ehlers-Danlos syndrome, classic type, 1	2022-01-05	criteria provided, single submitter	clinical testing	COL5A1 NM_000093.3 exon 30 p.Asn852Ser (c.2555A>G): This variant has not been reported in the literature but is present in 0.05% (7/15292) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/9-134785059-A-G?dataset=gnomad_r3). This variant is present in ClinVar, with classifications ranging from likely benign to Uncertain significance (Variation ID:365717). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics	RCV002429333	SCV002742975	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
PreventionGenetics, part of Exact Sciences	RCV003902426	SCV004721886	likely benign	COL5A1-related disorder	2022-12-20	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).