Submissions for variant NM_000093.5(COL5A1):c.574G>A (p.Asp192Asn)

gnomAD frequency: 0.02227  dbSNP: rs138579182

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124479	SCV000167912	benign	not specified	2013-01-09	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	RCV001507169	SCV000283504	benign	Ehlers-Danlos syndrome, classic type, 1	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000124479	SCV000302245	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000319752	SCV000478507	likely benign	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588510	SCV000603172	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588510	SCV000695401	benign	not provided	2017-03-10	criteria provided, single submitter	clinical testing	Variant summary: The COL5A1 c.574G>A (p.Asp192Asn) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 2009/119100 control chromosomes (28 homozygotes) at a frequency of 0.0168682, which is approximately 13495 times the estimated maximal expected allele frequency of a pathogenic COL5A1 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 it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Ambry Genetics	RCV002312848	SCV000738316	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-05	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000226247	SCV000781254	likely benign	Ehlers-Danlos syndrome, classic type	2016-11-01	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000226247	SCV000803510	benign	Ehlers-Danlos syndrome, classic type	2018-05-31	criteria provided, single submitter	curation	This variant is interpreted as a Benign - Stand Alone, for Ehlers-Danlos syndrome, classic type, 1, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BP5 => Variant found in a case with an alternate molecular basis for disease. BA1 => Allele frequency is >1% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. Allele frequency is >4% in European (Finnish).
Genome-Nilou Lab	RCV001507169	SCV002554049	benign	Ehlers-Danlos syndrome, classic type, 1	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002269919	SCV002554050	benign	Fibromuscular dysplasia, multifocal	2022-03-15	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277225	SCV002565783	benign	Ehlers-Danlos syndrome	2022-06-10	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000124479	SCV001808529	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000124479	SCV001931239	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000124479	SCV001975725	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000124479	SCV002036268	benign	not specified		no assertion criteria provided	clinical testing