Submissions for variant NM_000089.4(COL1A2):c.1383C>T (p.Pro461=)

gnomAD frequency: 0.00120  dbSNP: rs139726213

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029592	SCV000052244	likely benign	Osteogenesis imperfecta	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Likely benign.
Invitae	RCV000541643	SCV000627292	benign	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2024-01-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000611702	SCV000717238	likely benign	not specified	2018-01-08	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.
Illumina Laboratory Services, Illumina	RCV000029592	SCV001322822	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001160980	SCV001322823	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000029592	SCV002564769	likely benign	Osteogenesis imperfecta	2020-11-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381266	SCV002699855	benign	Cardiovascular phenotype	2021-07-19	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.
Fulgent Genetics, Fulgent Genetics	RCV002477016	SCV002797926	likely benign	Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Ehlers-Danlos syndrome, cardiac valvular type; Osteoporosis; Ehlers-danlos syndrome, arthrochalasia type, 2; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2	2021-09-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003430642	SCV004162525	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	COL1A2: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003924864	SCV004742425	likely benign	COL1A2-related disorder	2019-04-17	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).