Submissions for variant NM_000393.5(COL5A2):c.2741C>T (p.Ala914Val) (rs201486858)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000196083	SCV000249953	uncertain significance	not provided	2017-09-06	criteria provided, single submitter	clinical testing	The A914V variant in the COL5A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A914V variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A914V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret A914V as a variant of uncertain significance.
Ambry Genetics	RCV000251071	SCV000319649	uncertain significance	Cardiovascular phenotype	2019-05-02	criteria provided, single submitter	clinical testing	The p.A914V variant (also known as c.2741C>T), located in coding exon 41 of the COL5A2 gene, results from a C to T substitution at nucleotide position 2741. The alanine at codon 914 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Clinical Services Laboratory,Illumina	RCV000396728	SCV000425636	uncertain significance	Ehlers-Danlos syndrome, type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000457016	SCV000547884	likely benign	Ehlers-Danlos syndrome, classic type	2019-12-31	criteria provided, single submitter	clinical testing
Fulgent Genetics,Fulgent Genetics	RCV000457016	SCV000895374	uncertain significance	Ehlers-Danlos syndrome, classic type	2018-10-31	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000196083	SCV001153242	uncertain significance	not provided	2019-03-01	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001143727	SCV001304276	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.