Submissions for variant NM_000393.5(COL5A2):c.1535T>C (p.Val512Ala)

gnomAD frequency: 0.01792  dbSNP: rs35852101

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124500	SCV000167933	benign	not specified	2012-12-11	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	RCV000205712	SCV000262015	benign	Ehlers-Danlos syndrome, classic type, 1	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000124500	SCV000303977	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000372149	SCV000425647	likely benign	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000999941	SCV000603196	benign	Ehlers-Danlos syndrome, classic type, 2	2023-11-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589740	SCV000696670	benign	not provided	2017-03-21	criteria provided, single submitter	clinical testing	Variant summary: The COL5A2 c.1535T>C (p.Val512Ala) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. The variant does not lie within a known functional domain (InterPro) and 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in the large control database ExAC at a frequency of 0.0182311 (2213/121386 control chromosomes [34 homozygotes]), which is approximately 14585 times the estimated maximal expected allele frequency of a pathogenic COL5A2 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Ambry Genetics	RCV002312858	SCV000738327	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-08-07	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV000999941	SCV001299566	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000589740	SCV002563649	benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	COL5A2: BS1, BS2
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277231	SCV002565802	benign	Ehlers-Danlos syndrome	2022-07-16	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000124500	SCV001808617	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000124500	SCV001927980	benign	not specified		no assertion criteria provided	clinical testing