Submissions for variant NM_000089.4(COL1A2):c.2168A>G (p.Asn723Ser)

gnomAD frequency: 0.00016  dbSNP: rs189374343

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000404554	SCV000470605	likely benign	Osteogenesis imperfecta	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.
Illumina Laboratory Services, Illumina	RCV000307937	SCV000470606	benign	Ehlers-danlos syndrome, arthrochalasia 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.
Invitae	RCV002229911	SCV000627310	likely benign	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2024-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001718783	SCV000725707	likely benign	not provided	2020-10-08	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659378	SCV000781189	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001718783	SCV002048991	uncertain significance	not provided	2021-02-17	criteria provided, single submitter	clinical testing	The COL1A2 c.2168A>G; p.Asn723Ser variant (rs189374343), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 360961). This variant is found in the general population with an overall allele frequency of 0.017% (47/282806 alleles) in the Genome Aggregation Database. The asparagine at codon 723 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.178). Due to limited information, the clinical significance of the p.Asn723Ser variant is uncertain at this time.
Ambry Genetics	RCV002429325	SCV002731351	uncertain significance	Cardiovascular phenotype	2020-12-31	criteria provided, single submitter	clinical testing	The p.N723S variant (also known as c.2168A>G), located in coding exon 36 of the COL1A2 gene, results from an A to G substitution at nucleotide position 2168. The asparagine at codon 723 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.