Submissions for variant NM_000089.4(COL1A2):c.304C>T (p.Pro102Ser)

gnomAD frequency: 0.00060  dbSNP: rs189557655

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000710783	SCV000516946	likely benign	not provided	2024-09-17	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000440701	SCV000603114	likely benign	not specified	2019-06-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080558	SCV000627332	benign	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2025-02-02	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000710783	SCV000703498	uncertain significance	not provided	2016-12-19	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659368	SCV000781179	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710783	SCV000841087	benign	not provided	2017-11-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001159491	SCV001321209	benign	Osteogenesis imperfecta	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001159492	SCV001321210	likely benign	Ehlers-Danlos syndrome, arthrochalasia type, 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001159491	SCV002564791	likely benign	Osteogenesis imperfecta	2021-04-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278662	SCV002565582	likely benign	Ehlers-Danlos syndrome	2021-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002446665	SCV002754115	likely benign	Cardiovascular phenotype	2019-05-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen	RCV000710783	SCV005433464	uncertain significance	not provided	2024-11-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000440701	SCV005885185	likely benign	not specified	2025-02-25	criteria provided, single submitter	clinical testing	Variant summary: COL1A2 c.304C>T (p.Pro102Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0006 in 251452 control chromosomes, predominantly at a frequency of 0.001 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 36 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL1A2 causing Osteogenesis Imperfecta phenotype (2.8e-05). c.304C>T has been reported in the literature in individuals affected with Osteogenesis Imperfecta (e.g. Lindahl_2015). This report does not provide unequivocal conclusions about association of the variant with Osteogenesis Imperfecta. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 25944380). ClinVar contains an entry for this variant (Variation ID: 379658). Based on the evidence outlined above, the variant was classified as likely benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000710783	SCV001807438	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000710783	SCV001968285	likely benign	not provided		no assertion criteria provided	clinical testing